The osteocyte: an endocrine cell ... and more.

Few investigators think of bone as an endocrine gland, even after the discovery that osteocytes produce circulating fibroblast growth factor 23 that targets the kidney and potentially other organs. In fact, until the last few years, osteocytes were perceived by many as passive, metabolically inactive cells. However, exciting recent discoveries have shown that osteocytes encased within mineralized bone matrix are actually multifunctional cells with many key regulatory roles in bone and mineral homeostasis. In addition to serving as endocrine cells and regulators of phosphate homeostasis, these cells control bone remodeling through regulation of both osteoclasts and osteoblasts, are mechanosensory cells that coordinate adaptive responses of the skeleton to mechanical loading, and also serve as a manager of the bone's reservoir of calcium. Osteocytes must survive for decades within the bone matrix, making them one of the longest lived cells in the body. Viability and survival are therefore extremely important to ensure optimal function of the osteocyte network. As we continue to search for new therapeutics, in addition to the osteoclast and the osteoblast, the osteocyte should be considered in new strategies to prevent and treat bone disease.

[1]  P. Kostenuik,et al.  The Receptor Activator of Nuclear Factor-κB Ligand Inhibitor Osteoprotegerin Is a Bone-Protective Agent in a Rat Model of Chronic Renal Insufficiency and Hyperparathyroidism , 2005, Calcified Tissue International.

[2]  E. Bonucci,et al.  Detection of osteoprotegerin (OPG) and its ligand (RANKL) mRNA and protein in femur and tibia of the rat , 2005, Journal of Molecular Histology.

[3]  J. Wergedal,et al.  Bone formation by osteocytes. , 1971, The American journal of physiology.

[4]  R. Takagi,et al.  FGF23 is mainly synthesized by osteocytes in the regularly distributed osteocytic lacunar canalicular system established after physiological bone remodeling. , 2009, Journal of electron microscopy.

[5]  Hang Lee,et al.  Regulation of C‐Terminal and Intact FGF‐23 by Dietary Phosphate in Men and Women , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  Z. Massy,et al.  FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages , 2012, Osteoporosis International.

[7]  R. Jilka,et al.  Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. , 2005, Endocrinology.

[8]  Yi Duan,et al.  An Integrative Review of Mechanotransduction in Endothelial, Epithelial (Renal) and Dendritic Cells (Osteocytes) , 2011, Cellular and molecular bioengineering.

[9]  A. van der Plas,et al.  Sensitivity of osteocytes to biomechanical stress in vitro , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  Xi Jiang,et al.  Dentin matrix protein 1 expression during osteoblastic differentiation, generation of an osteocyte GFP-transgene. , 2004, Bone.

[11]  L. Bonewald,et al.  The Amazing Osteocyte , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[12]  G. Åkerström,et al.  Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. , 2007, The Journal of endocrinology.

[13]  L. Bonewald,et al.  Glucocorticoid dose determines osteocyte cell fate , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  T. Page,et al.  Rat-specific decreases in platelet count caused by a humanized monoclonal antibody against sclerostin. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[15]  N. Sharkey,et al.  Enhanced Osteoclastic Resorption and Responsiveness to Mechanical Load in Gap Junction Deficient Bone , 2011, PloS one.

[16]  E. Burger,et al.  DNA fragmentation during bone formation in neonatal rodents assessed by transferase‐mediated end labeling , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  L. Quarles,et al.  Distinct roles for intrinsic osteocyte abnormalities and systemic factors in regulation of FGF23 and bone mineralization in Hyp mice. , 2007, American journal of physiology. Endocrinology and metabolism.

[18]  Kosaku Kurata,et al.  Bone Marrow Cell Differentiation Induced by Mechanically Damaged Osteocytes in 3D Gel‐Embedded Culture , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[19]  K. Jepsen,et al.  Osteocyte apoptosis and control of bone resorption following ovariectomy in mice. , 2010, Bone.

[20]  Lynda F. Bonewald,et al.  Osteocyte Wnt/β-Catenin Signaling Is Required for Normal Bone Homeostasis , 2010, Molecular and Cellular Biology.

[21]  J. Laurence,et al.  Degradation of MEPE, DMP1, and release of SIBLING ASARM-peptides (minhibins): ASARM-peptide(s) are directly responsible for defective mineralization in HYP. , 2008, Endocrinology.

[22]  Di Chen,et al.  MEPE has the properties of an osteoblastic phosphatonin and minhibin. , 2004, Bone.

[23]  M. Mohammadi,et al.  The parathyroid is a target organ for FGF23 in rats. , 2007, The Journal of clinical investigation.

[24]  Gary S Stein,et al.  The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. , 2004, Molecular endocrinology.

[25]  J. Stock,et al.  Targeted Disruption of the Osteoblast/Osteocyte Factor 45 Gene (OF45) Results in Increased Bone Formation and Bone Mass* , 2003, The Journal of Biological Chemistry.

[26]  T. Hentunen,et al.  Death of osteocytes turns off the inhibition of osteoclasts and triggers local bone resorption. , 2005, Biochemical and biophysical research communications.

[27]  S. Cowin,et al.  A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. , 1994, Journal of biomechanics.

[28]  A. Parfitt,et al.  Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. , 1998, The Journal of clinical investigation.

[29]  L. Bélanger,et al.  Technical approaches leading to the concept of osteocytic osteolysis. , 1967, Clinical orthopaedics and related research.

[30]  S. Vilaró,et al.  Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes. , 1999, Journal of cell science.

[31]  Gregory F Weber,et al.  Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels , 2012, Proceedings of the National Academy of Sciences.

[32]  Masaaki Inaba,et al.  Increased osteocyte death and mineralization inside bone after parathyroidectomy in patients with secondary hyperparathyroidism , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[33]  E. Bonucci,et al.  Osteocyte ultrastructure in renal osteodystrophy , 1977, Virchows Archiv A.

[34]  Masaki Hojo,et al.  Calcium response in single osteocytes to locally applied mechanical stimulus: differences in cell process and cell body. , 2009, Journal of biomechanics.

[35]  Mark L. Johnson,et al.  Activation of β-catenin signaling in MLO-Y4 osteocytic cells versus 2T3 osteoblastic cells by fluid flow shear stress and PGE2: Implications for the study of mechanosensation in bone. , 2010, Bone.

[36]  W. R. Thompson,et al.  Association of the α2δ1 subunit with Cav3.2 enhances membrane expression and regulates mechanically induced ATP release in MLO‐Y4 osteocytes , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[37]  T. Nagata,et al.  Effect of prostaglandin E2 on mineralization of bone nodules formed by fetal rat calvarial cells , 1994, Calcified Tissue International.

[38]  Extracellular calcium causes the release of calcium from intracellular stores in chick osteocytes. , 1995, Biochemical and biophysical research communications.

[39]  Ivan Lobov,et al.  Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor , 2002, The Journal of cell biology.

[40]  J. Aubin,et al.  Individual osteoblasts in the developing calvaria express different gene repertoires. , 2001, Bone.

[41]  S. Reppe,et al.  Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[42]  John A Latham,et al.  Osteocyte control of bone formation via sclerostin, a novel BMP antagonist , 2003, The EMBO journal.

[43]  Christopher R Jacobs,et al.  Primary cilium‐dependent mechanosensing is mediated by adenylyl cyclase 6 and cyclic AMP in bone cells , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[44]  W. Jee,et al.  Sclerostin antibody increases bone mass by stimulating bone formation and inhibiting bone resorption in a hindlimb-immobilization rat model. , 2011, Bone.

[45]  A. Walser,et al.  Structure and functions of osteocytes in normal conditions and under the influence of parathyroid extract , 1968 .

[46]  C. Jacobs,et al.  A role for the primary cilium in paracrine signaling between mechanically stimulated osteocytes and mesenchymal stem cells. , 2011, Biochemical and biophysical research communications.

[47]  Olivier Verborgt,et al.  Spatial Distribution of Bax and Bcl‐2 in Osteocytes After Bone Fatigue: Complementary Roles in Bone Remodeling Regulation? , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[48]  Jiliang Li,et al.  Risedronate and alendronate suppress osteocyte apoptosis following cyclic fatigue loading. , 2007, Bone.

[49]  A. Kuijpers-Jagtman,et al.  Inhibition of osteocyte apoptosis by fluid flow is mediated by nitric oxide. , 2008, Biochemical and biophysical research communications.

[50]  H. Yoshikawa,et al.  Oxygen tension is an important mediator of the transformation of osteoblasts to osteocytes , 2007, Journal of Bone and Mineral Metabolism.

[51]  G. Marotti,et al.  Morphological study of intercellular junctions during osteocyte differentiation. , 1990, Bone.

[52]  P. Kostenuik,et al.  Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[53]  A. Parfitt,et al.  Osteoblast Programmed Cell Death (Apoptosis): Modulation by Growth Factors and Cytokines , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[54]  Jean X. Jiang,et al.  Gap junction and hemichannel functions in osteocytes. , 2013, Bone.

[55]  L. Bonewald,et al.  Establishment of an Osteocyte‐like Cell Line, MLO‐Y4 , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[56]  W. Fraser,et al.  Serum MEPE-ASARM-peptides are elevated in X-linked rickets (HYP): implications for phosphaturia and rickets. , 2004, The Journal of endocrinology.

[57]  L. Bonewald,et al.  Cell line IDG‐SW3 replicates osteoblast‐to‐late‐osteocyte differentiation in vitro and accelerates bone formation in vivo , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[58]  D. Megías,et al.  Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition , 2006, Journal of Cell Science.

[59]  Y. Takeuchi,et al.  Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. , 2004, The Journal of clinical investigation.

[60]  J. D. Spencer,et al.  The femoral head in osteonecrosis. A quantitative study of osteocyte population. , 1989, The Journal of bone and joint surgery. British volume.

[61]  E. Canalis,et al.  Effects of prostaglandin E2 on bone formation in cultured fetal rat calvariae: role of insulin-like growth factor-I. , 1993, Endocrinology.

[62]  T. Gross,et al.  Osteocyte hypoxia: a novel mechanotransduction pathway. , 1999, American journal of physiology. Cell physiology.

[63]  Sheldon Weinbaum,et al.  Fluid and Solute Transport in Bone: Flow-Induced Mechanotransduction. , 2009, Annual review of fluid mechanics.

[64]  I. J. Singh,et al.  The effects of cold‐stress, hibernation, and prolonged inactivity on bone dynamics in the golden hamster, Mesocricetus auratus , 1981, Journal of morphology.

[65]  D. Rowe,et al.  Use of Type I Collagen Green Fluorescent Protein Transgenes to Identify Subpopulations of Cells at Different Stages of the Osteoblast Lineage , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[66]  Zhousheng Xiao,et al.  Kif3a Deficiency Reverses the Skeletal Abnormalities in Pkd1 Deficient Mice by Restoring the Balance Between Osteogenesis and Adipogenesis , 2010, PloS one.

[67]  P. Kostenuik,et al.  Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. , 2006, Bone.

[68]  L. Lind,et al.  Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. , 2009, Atherosclerosis.

[69]  O. Kennedy,et al.  Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations. , 2012, Bone.

[70]  Teruko Takano-Yamamoto,et al.  Terminal Differentiation of Osteoblasts to Osteocytes Is Accompanied by Dramatic Changes in the Distribution of Actin‐Binding Proteins , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[71]  K. White,et al.  FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. , 2003, The Journal of clinical investigation.

[72]  C. Xian,et al.  The role of osteocyte apoptosis in cancer chemotherapy‐induced bone loss , 2012, Journal of cellular physiology.

[73]  J. Reeve,et al.  The FASEB Journal express article 10.1096/fj.05-4221fje. Published online August 25, 2005. ©2005 FASEB , 2022 .

[74]  A. Evdokiou,et al.  Sclerostin is a locally acting regulator of late‐osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE‐ASARM‐dependent mechanism , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[75]  L. Bonewald,et al.  DMP1-targeted Cre Expression in Odontoblasts and Osteocytes , 2007, Journal of dental research.

[76]  T. C. Lee,et al.  RANKL and OPG activity is regulated by injury size in networks of osteocyte-like cells. , 2011, Bone.

[77]  S. Manolagas,et al.  Glucocorticoids Induce Osteocyte Apoptosis by Blocking Focal Adhesion Kinase-mediated Survival , 2007, Journal of Biological Chemistry.

[78]  Matthew J Silva,et al.  Attenuated Response to In Vivo Mechanical Loading in Mice With Conditional Osteoblast Ablation of the Connexin43 Gene (Gja1) , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[79]  R. Weinstein,et al.  Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. , 2004, Endocrinology.

[80]  P. Nijweide,et al.  Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts--correlation with prostaglandin upregulation. , 1995, Biochemical and biophysical research communications.

[81]  L. You,et al.  Apoptotic osteocytes regulate osteoclast precursor recruitment and differentiation in vitro , 2011, Journal of cellular biochemistry.

[82]  I. D. Padhi,et al.  Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. , 2010, The Journal of clinical endocrinology and metabolism.

[83]  K. Tracey,et al.  HMGB1 is a bone‐active cytokine , 2008, Journal of cellular physiology.

[84]  Y. Mishina,et al.  The Dentin Matrix Protein 1 (Dmp1) is Specifically Expressed in Mineralized, but not Soft, Tissues during Development , 2003, Journal of dental research.

[85]  C. Baud,et al.  Structural changes of the periosteocytic area inVipera aspis (L.) (Ophidia, viperidae) bone tissue in various physiological conditions , 2007, Calcified Tissue International.

[86]  B. Kream,et al.  Regulation of bone formation (second of two parts). , 1983, The New England journal of medicine.

[87]  N. Rushton,et al.  Patterns of osteocytic endothelial nitric oxide synthase expression in the femoral neck cortex: differences between cases of intracapsular hip fracture and controls. , 2002, Bone.

[88]  L. Bonewald,et al.  Prostaglandin E2: from clinical applications to its potential role in bone- muscle crosstalk and myogenic differentiation. , 2012, Recent patents on biotechnology.

[89]  B. Noble,et al.  Apoptotic Bodies Convey Activity Capable of Initiating Osteoclastogenesis and Localized Bone Destruction , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[90]  D. Galas,et al.  Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. , 2001, American journal of human genetics.

[91]  K. Wenger,et al.  Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading. , 2007, Bone.

[92]  N. Forest,et al.  How osteoblasts become osteocytes: a decreasing matrix forming process. , 1991, Journal de biologie buccale.

[93]  J. Wolff Das Gesetz der Transformation der Knochen , 1893 .

[94]  J. Heersche,et al.  Effects of hind limb unloading and reloading on nitric oxide synthase expression and apoptosis of osteocytes and chondrocytes. , 2006, Bone.

[95]  C. O’Brien,et al.  A Novel Ligand-independent Function of the Estrogen Receptor Is Essential for Osteocyte and Osteoblast Mechanotransduction* , 2007, Journal of Biological Chemistry.

[96]  F. Recklinghausen,et al.  Untersuchungen über Rachitis und Osteomalacie , 1910 .

[97]  M. Mcguire,et al.  Expression of parathyroid hormone‐related peptide (PTHrP) and its receptor (PTH1R) during the histogenesis of cartilage and bone in the chicken mandibular process , 2002, Journal of anatomy.

[98]  L. Bonewald,et al.  Conditional deletion of Pkd1 in osteocytes disrupts skeletal mechanosensing in mice , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[99]  Mark L. Johnson,et al.  Osteocytes, mechanosensing and Wnt signaling. , 2008, Bone.

[100]  R. Weinstein,et al.  Connexin 43 Is Required for the Anti‐Apoptotic Effect of Bisphosphonates on Osteocytes and Osteoblasts In Vivo , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[101]  A. van der Plas,et al.  Characteristics and properties of osteocytes in culture , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[102]  B. Pedersen,et al.  LIF is a contraction-induced myokine stimulating human myocyte proliferation. , 2011, Journal of applied physiology.

[103]  Daniel P Nicolella,et al.  Osteocyte lacunae tissue strain in cortical bone. , 2006, Journal of biomechanics.

[104]  Peng Liu,et al.  Sclerostin Binds to LRP5/6 and Antagonizes Canonical Wnt Signaling* , 2005, Journal of Biological Chemistry.

[105]  B. Hall,et al.  Buried alive: How osteoblasts become osteocytes , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[106]  M. Robinson,et al.  Sclerostin antibody treatment enhances bone strength but does not prevent growth retardation in young mice treated with dexamethasone. , 2011, Arthritis and rheumatism.

[107]  H. Ris,et al.  Osteocyte Shape Is Dependent on Actin Filaments and Osteocyte Processes Are Unique Actin‐Rich Projections , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[108]  H. Birkedal‐Hansen,et al.  The metalloproteinase MT1-MMP is required for normal development and maintenance of osteocyte processes in bone , 2005, Journal of Cell Science.

[109]  D. Lacey,et al.  Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[110]  Shiqin Zhang,et al.  Cilia-like Structures and Polycystin-1 in Osteoblasts/Osteocytes and Associated Abnormalities in Skeletogenesis and Runx2 Expression* , 2006, Journal of Biological Chemistry.

[111]  D. C. Genetos,et al.  Hypoxic osteocytes recruit human MSCs through an OPN/CD44-mediated pathway. , 2008, Biochemical and biophysical research communications.

[112]  T. Takano-Yamamoto,et al.  A three-dimensional distribution of osteocyte processes revealed by the combination of confocal laser scanning microscopy and differential interference contrast microscopy. , 2001, Bone.

[113]  M. Kasper,et al.  Immunohistochemical investigations on the differentiation marker protein E11 in rat calvaria, calvaria cell culture and the osteoblastic cell line ROS 17/2.8 , 1999, Histochemistry and Cell Biology.

[114]  A. Pitsillides,et al.  Osteocytes Use Estrogen Receptor α to Respond to Strain but Their ERα Content Is Regulated by Estrogen , 2006 .

[115]  L. Bonewald,et al.  The Biological Function of DMP-1 in Osteocyte Maturation Is Mediated by Its 57-kDa C-terminal Fragment , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[116]  L. Bonewald,et al.  Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism , 2006, Nature Genetics.

[117]  S. Ejiri,et al.  Matrix Mineralization as a Trigger for Osteocyte Maturation , 2008, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[118]  P. Stern,et al.  Bone Anabolic Responses to Mechanical Load In Vitro Involve COX-2 and Constitutive NOS , 2004, Connective tissue research.

[119]  H. Melhus,et al.  Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. , 2009, Atherosclerosis.

[120]  M. V. Bennett,et al.  Gap junctions, electrotonic coupling, and intercellular communication. , 1978, Neurosciences Research Program bulletin.

[121]  H. Higaki,et al.  Evidence for the role of osteocytes in the initiation of targeted remodeling. , 2009, Technology and health care : official journal of the European Society for Engineering and Medicine.

[122]  Anne Marie Kuijpers-Jagtman,et al.  Osteocytes subjected to fluid flow inhibit osteoclast formation and bone resorption. , 2007, Bone.

[123]  L. Bonewald,et al.  Dentin Matrix Protein 1 Gene Cis-regulation , 2005, Journal of Biological Chemistry.

[124]  W. Jee,et al.  Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats. , 2010, Bone.

[125]  Y Wang,et al.  Effects of nanomechanical bone tissue properties on bone tissue strain: implications for osteocyte mechanotransduction. , 2008, Journal of musculoskeletal & neuronal interactions.

[126]  G. Passeri,et al.  Cell autonomous requirement of connexin 43 for osteocyte survival: Consequences for endocortical resorption and periosteal bone formation , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[127]  L. Quarles,et al.  Regulation of Fibroblastic Growth Factor 23 Expression but Not Degradation by PHEX* , 2003, Journal of Biological Chemistry.

[128]  B. Lanske,et al.  Characterization and cloning of the E11 antigen, a marker expressed by rat osteoblasts and osteocytes. , 1996, Bone.

[129]  C. Gordon,et al.  Efficacy and Harms of Nasal Calcitonin in Improving Bone Density in Young Patients With Inflammatory Bowel Disease: A Randomized, Placebo-Controlled, Double-Blind Trial , 2011, The American Journal of Gastroenterology.

[130]  Matthew R Allen,et al.  Mechanical Stimulation of Bone in Vivo Reduces Osteocyte Expression of Sost/Sclerostin* , 2008, Journal of Biological Chemistry.

[131]  Y. Yamaguchi,et al.  Isolated chick osteocytes stimulate formation and bone-resorbing activity of osteoclast-like cells , 2005, Journal of Bone and Mineral Metabolism.

[132]  H. Tenenhouse,et al.  Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. , 2005, Endocrinology.

[133]  L. Bonewald,et al.  Glucocorticoid-Induced Autophagy in Osteocytes , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[134]  B. Komm,et al.  The Wnt antagonist secreted frizzled‐related protein‐1 controls osteoblast and osteocyte apoptosis , 2005, Journal of cellular biochemistry.

[135]  P. Lips,et al.  Histomorphometric analysis reveals reduced bone mass and bone formation in patients with quiescent Crohn's disease. , 2011, Gastroenterology.

[136]  Melissa L. Knothe Tate,et al.  Whither flows the fluid in bone?" An osteocyte's perspective. , 2003 .

[137]  A. Schulz,et al.  Activity of osteoclastic bone resorption in primary hyperparathyroidism — a comparative electron microscopic and histomorphometric study , 1976, Calcified Tissue Research.

[138]  A. Pitsillides,et al.  Extracellular Matrix Mineralization Promotes E11/gp38 Glycoprotein Expression and Drives Osteocytic Differentiation , 2012, PloS one.

[139]  M. Zimny,et al.  Effects of Hibernation on Interradicular Alveolar Bone , 1977, Journal of dental research.

[140]  S. Toyosawa,et al.  Eccentric Localization of Osteocytes Expressing Enzymatic Activities, Protein, and mRNA Signals for Type 5 Tartrate-resistant Acid Phosphatase (TRAP) , 2004, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[141]  L. Bonewald Establishment and characterization of an osteocyte-like cell line, MLO-Y4 , 1999, Journal of Bone and Mineral Metabolism.

[142]  Matthew R Allen,et al.  Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. , 2012, Bone.

[143]  Y. Tsutsumi,et al.  Association of CD44 with OTS-8 in tumor vascular endothelial cells. , 2000, Biochimica et biophysica acta.

[144]  S. Krane,et al.  Osteocyte and osteoblast apoptosis and excessive bone deposition accompany failure of collagenase cleavage of collagen. , 2000, The Journal of clinical investigation.

[145]  G. Frankel,et al.  Metallurgy (communication arising): Stainless-steel corrosion and MnS inclusions , 2003, Nature.

[146]  M. Fukayama,et al.  Podoplanin is regulated by AP-1 and promotes platelet aggregation and cell migration in osteosarcoma. , 2011, The American journal of pathology.

[147]  Establishment and hormonal regulation of a conditionally transformed preosteocytic cell line from adult human bone. , 1996, Endocrinology.

[148]  Hai Qing,et al.  Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[149]  B. Komm,et al.  Transcriptional profiling of human osteoblast differentiation , 2003, Journal of cellular biochemistry.

[150]  L. Bonewald,et al.  Effects of Mechanical Strain on the Function of Gap Junctions in Osteocytes Are Mediated through the Prostaglandin EP2 Receptor* , 2003, Journal of Biological Chemistry.

[151]  M. Quintanilla,et al.  Regulation of podoplanin/PA2.26 antigen expression in tumour cells. Involvement of calpain-mediated proteolysis. , 2009, The international journal of biochemistry & cell biology.

[152]  S. Harris,et al.  Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses. , 2011, The Journal of endocrinology.

[153]  R. Duncan,et al.  Fluid Shear‐Induced ATP Secretion Mediates Prostaglandin Release in MC3T3‐E1 Osteoblasts , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[154]  L. Quarles,et al.  Phosphorylated acidic serine-aspartate-rich MEPE-associated motif peptide from matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with homologies to endopeptidases on the X-chromosome enzyme activity. , 2007, The Journal of endocrinology.

[155]  A. Go,et al.  FGF23 induces left ventricular hypertrophy. , 2011, The Journal of clinical investigation.

[156]  E. Bonucci,et al.  Effects of intermittent parathyroid hormone (PTH) administration on SOST mRNA and protein in rat bone , 2007, Journal of Molecular Histology.

[157]  L. Raisz,et al.  Prostaglandins in bone: bad cop, good cop? , 2010, Trends in Endocrinology & Metabolism.

[158]  A. Poustka,et al.  A gene (PEX) with homologies to endopeptidases is mutated in patients with X–linked hypophosphatemic rickets , 1995, Nature Genetics.

[159]  Sheldon Weinbaum,et al.  Mechanotransduction and strain amplification in osteocyte cell processes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[160]  O. Verborgt,et al.  Loss of Osteocyte Integrity in Association with Microdamage and Bone Remodeling After Fatigue In Vivo , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[161]  M. HELLER-STEINBERG,et al.  Ground substance, bone salts, and cellular activity in bone formation and destruction. , 1951, The American journal of anatomy.

[162]  R. Bacabac,et al.  Tumor necrosis factor alpha and interleukin-1beta modulate calcium and nitric oxide signaling in mechanically stimulated osteocytes. , 2009, Arthritis and rheumatism.

[163]  L. Ferrucci,et al.  Relationship of serum fibroblast growth factor 23 with cardiovascular disease in older community-dwelling women. , 2011, European journal of endocrinology.

[164]  A. Boskey,et al.  MEPE’s Diverse Effects on Mineralization , 2009, Calcified Tissue International.

[165]  M Dioszegi,et al.  Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). , 2001, Human molecular genetics.

[166]  S. Manolagas,et al.  Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. , 2000, Endocrine reviews.

[167]  H. Dvorak,et al.  T1α/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema , 2003, The EMBO journal.

[168]  J. Shaughnessy,et al.  Inhibiting Dickkopf‐1 (Dkk1) Removes Suppression of Bone Formation and Prevents the Development of Osteolytic Bone Disease in Multiple Myeloma , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[169]  J. Reeve,et al.  NOS Isoforms in Adult Human Osteocytes: Multiple Pathways of NO Regulation? , 2004, Calcified Tissue International.

[170]  A. Hedge,et al.  Matrix extracellular phosphoglycoprotein (MEPE) is a new bone renal hormone and vascularization modulator. , 2009, Endocrinology.

[171]  G. Marotti,et al.  Quantitative evaluation on osteocyte canalicular density in human secondary osteons. , 1995, Bone.

[172]  Y. Mikuni‐Takagaki,et al.  Distinct responses of different populations of bone cells to mechanical stress. , 1996, Endocrinology.

[173]  Stephen B Doty,et al.  Delineating bone's interstitial fluid pathway in vivo. , 2004, Bone.

[174]  D. Woodbury,et al.  The effects of prostaglandin E2 in growing rats: Increased metaphyseal hard tissue and cortico-endosteal bone formation , 2007, Calcified Tissue International.

[175]  T. Hentunen,et al.  Conditioned medium from osteocytes stimulates the proliferation of bone marrow mesenchymal stem cells and their differentiation into osteoblasts. , 2004, Experimental cell research.

[176]  L. Bonewald,et al.  Unique Roles of Phosphorus in Endochondral Bone Formation and Osteocyte Maturation , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[177]  M. Giacca,et al.  A novel animal model to study non-spontaneous bisphosphonates osteonecrosis of jaw. , 2010, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[178]  M. McKee,et al.  MEPE‐ASARM Peptides Control Extracellular Matrix Mineralization by Binding to Hydroxyapatite: An Inhibition Regulated by PHEX Cleavage of ASARM , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[179]  D. Rowe,et al.  Identification of differentially expressed genes between osteoblasts and osteocytes. , 2009, Bone.

[180]  Jian Q. Feng,et al.  Dentin Matrix Protein 1, a Target Molecule for Cbfa1 in Bone, Is a Unique Bone Marker Gene , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[181]  R. Unwin,et al.  Matrix extracellular phosphoglycoprotein causes phosphaturia in rats by inhibiting tubular phosphate reabsorption. , 2007, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[182]  L. Bonewald,et al.  Identification of osteocyte‐selective proteins , 2010, Proteomics.

[183]  M. J. Pead,et al.  Indomethacin modulation of load-related stimulation of new bone formationin vivo , 2007, Calcified Tissue International.

[184]  J. Zwerina,et al.  Neutralisation of Dkk-1 protects from systemic bone loss during inflammation and reduces sclerostin expression , 2010, Annals of the rheumatic diseases.

[185]  T. Komori,et al.  Dentin Matrix Protein 1 Is Predominantly Expressed in Chicken and Rat Osteocytes But Not in Osteoblasts , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[186]  D. Zaffe,et al.  Osteocyte differentiation in the tibia of newborn rabbit: an ultrastructural study of the formation of cytoplasmic processes. , 1990, Acta anatomica.

[187]  Miikka Vikkula,et al.  LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development , 2001, Cell.

[188]  L. Bonewald,et al.  Mechanosensation and Transduction in Osteocytes. , 2006, BoneKEy osteovision.

[189]  G. Marotti The structure of bone tissues and the cellular control of their deposition. , 1996, Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia.

[190]  Christopher Price,et al.  Real-Time Measurement of Solute Transport Within the Lacunar-Canalicular System of Mechanically Loaded Bone: Direct Evidence for Load-Induced Fluid Flow , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[191]  L. Lind,et al.  Relationship between circulating FGF23 and total body atherosclerosis in the community. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[192]  T. Meitinger,et al.  Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23 , 2000, Nature Genetics.

[193]  P. Nijweide,et al.  Biochemical and histological studies on various bone cell preparations , 2006, Calcified Tissue International.

[194]  L. Bonewald,et al.  MLO‐Y4 Osteocyte‐Like Cells Support Osteoclast Formation and Activation , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[195]  L. Churchill,et al.  Matrix extracellular phosphoglycoprotein inhibits phosphate transport. , 2008, Journal of the American Society of Nephrology : JASN.

[196]  J M Polak,et al.  Mechanical Strain Stimulates Nitric Oxide Production by Rapid Activation of Endothelial Nitric Oxide Synthase in Osteocytes , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[197]  S. Doty Morphological evidence of gap junctions between bone cells , 2006, Calcified Tissue International.

[198]  Mai-Szu Wu,et al.  Fibroblast Growth Factor 23: A Possible Cause of Left Ventricular Hypertrophy in Hemodialysis Patients , 2009, The American journal of the medical sciences.

[199]  Minqi Li,et al.  Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. , 2007, Cell metabolism.

[200]  T. Meitinger,et al.  Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP). , 1997, Human molecular genetics.

[201]  S. Schulz,et al.  Immunohistochemical identification of the PTHR1 parathyroid hormone receptor in normal and neoplastic human tissues. , 2010, European journal of endocrinology.

[202]  Jenneke Klein-Nulend,et al.  Inhibition of Osteoclastogenesis by Mechanically Loaded Osteocytes: Involvement of MEPE , 2010, Calcified Tissue International.

[203]  M. Kneissel,et al.  SOST is a target gene for PTH in bone. , 2005, Bone.

[204]  L. Bonewald,et al.  Tissue strain amplification at the osteocyte lacuna: a microstructural finite element analysis. , 2007, Journal of biomechanics.

[205]  D. Rowe,et al.  Directing the expression of a green fluorescent protein transgene in differentiated osteoblasts: comparison between rat type I collagen and rat osteocalcin promoters. , 2002, Bone.

[206]  M. Mohammadi,et al.  FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. , 2009, American journal of physiology. Renal physiology.

[207]  E H Burger,et al.  The production of nitric oxide and prostaglandin E(2) by primary bone cells is shear stress dependent. , 2001, Journal of biomechanics.

[208]  J. Silver,et al.  PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. , 2010, American journal of physiology. Renal physiology.

[209]  P. Nijweide,et al.  Osteocyte‐Specific Monoclonal Antibody MAb OB7.3 Is Directed Against Phex Protein , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[210]  M. Edmonds,et al.  Thiazolidinediones induce osteocyte apoptosis and increase sclerostin expression , 2010, Diabetic medicine : a journal of the British Diabetic Association.

[211]  J. Aubin,et al.  The mature osteoblast phenotype is characterized by extensive plasticity. , 1997, Experimental cell research.

[212]  L. Bonewald,et al.  Establishment of an Osteoid Preosteocyte‐like Cell MLO‐A5 That Spontaneously Mineralizes in Culture , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[213]  J. Polak,et al.  Apoptosis--a significant cause of bone cell death in osteonecrosis of the femoral head. , 2004, The Journal of bone and joint surgery. British volume.

[214]  Toshitaka Nakamura,et al.  Role of Inducible Nitric Oxide Synthase in Skeletal Adaptation to Acute Increases in Mechanical Loading , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[215]  Ron Y Kwon,et al.  Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism , 2007, Proceedings of the National Academy of Sciences.

[216]  T. Shimada,et al.  Therapeutic Effects of Anti‐FGF23 Antibodies in Hypophosphatemic Rickets/Osteomalacia , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[217]  L. Bonewald,et al.  Gene expression signatures of a fibroblastoid preosteoblast and cuboidal osteoblast cell model compared to the MLO-Y4 osteocyte cell model. , 2009, Bone.

[218]  P. Roberson,et al.  Intermittent parathyroid hormone administration counteracts the adverse effects of glucocorticoids on osteoblast and osteocyte viability, bone formation, and strength in mice. , 2010, Endocrinology.

[219]  P. Roberson,et al.  Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. , 1999, The Journal of clinical investigation.

[220]  A. E. Espinoza Orías,et al.  Overexpression of DMP1 accelerates mineralization and alters cortical bone biomechanical properties in vivo. , 2012, Journal of the mechanical behavior of biomedical materials.

[221]  S. Krieger,et al.  Sp1/Sp3 and DNA-methylation contribute to basal transcriptional activation of human podoplanin in MG63 versus Saos-2 osteoblastic cells , 2007, BMC Molecular Biology.

[222]  M. Takagi,et al.  In situ Localization and in vitro Expression of Osteoblast/Osteocyte Factor 45 mRNA during Bone Cell Differentiation , 2002, The Histochemical Journal.

[223]  D. Fyhrie,et al.  Modulation of sclerostin expression by mechanical loading and bone morphogenetic proteins in osteogenic cells. , 2009, Biorheology.

[224]  T. Meitinger,et al.  Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked hypophosphatemia. , 1997, Human molecular genetics.

[225]  Bente Klarlund Pedersen,et al.  Muscles and their myokines , 2011, Journal of Experimental Biology.

[226]  Lynda F. Bonewald,et al.  Prostaglandin Promotion of Osteocyte Gap Junction Function through Transcriptional Regulation of Connexin 43 by Glycogen Synthase Kinase 3/β-Catenin Signaling , 2009, Molecular and Cellular Biology.

[227]  M. Inaba,et al.  FGF-23 in patients with end-stage renal disease on hemodialysis. , 2004, Kidney international.

[228]  L. Quarles,et al.  Inhibition of MEPE cleavage by Phex. , 2002, Biochemical and biophysical research communications.

[229]  R. Weinstein,et al.  Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. , 2000, The Journal of clinical endocrinology and metabolism.

[230]  M. Bouxsein,et al.  Control of Bone Mass and Remodeling by PTH Receptor Signaling in Osteocytes , 2008, PloS one.

[231]  M. Farach-Carson,et al.  Expression of voltage sensitive calcium channel (VSCC) L‐type Cav1.2 (α1C) and T‐type Cav3.2 (α1H) subunits during mouse bone development , 2005 .

[232]  G. Marotti,et al.  Osteocyte dendrogenesis in static and dynamic bone formation: an ultrastructural study. , 2004, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[233]  C. Ohlsson,et al.  Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis. , 2004, Endocrinology.

[234]  P. Mcneil,et al.  Role of muscle-derived growth factors in bone formation. , 2010, Journal of musculoskeletal & neuronal interactions.

[235]  L. Bélanger,et al.  PARATHORMONE-INDUCED OSTEOLYSIS IN DOGS. A MICRORADIOGRAPHIC AND ALPHARADIOGRAPHIC SURVEY. , 1964, The Journal of bone and joint surgery. American volume.

[236]  J. Aubin,et al.  Determination of numbers of osteoprogenitors present in isolated fetal rat calvaria cells in vitro. , 1989, Developmental biology.

[237]  B. Barlogie,et al.  Characterization of Wnt/β‐catenin signalling in osteoclasts in multiple myeloma , 2010, British journal of haematology.

[238]  P. Kostenuik,et al.  Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[239]  E. Russo,et al.  Jaw Osteonecrosis in Patients Treated with Bisphosphonates: An Ultrastructural Study , 2010, Ultrastructural pathology.

[240]  S. Kaptoge,et al.  Osteocytic Expression of Constitutive NO Synthase Isoforms in the Femoral Neck Cortex: A Case‐Control Study of Intracapsular Hip Fracture , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[241]  K. Metsikkö,et al.  Isolated primary osteocytes express functional gap junctions in vitro , 2006, Cell and Tissue Research.

[242]  Jiliang Li,et al.  The P2X7 Nucleotide Receptor Mediates Skeletal Mechanotransduction* , 2005, Journal of Biological Chemistry.

[243]  Daniel J Lightwood,et al.  Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[244]  P. Kostenuik,et al.  Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. , 2010, The Journal of clinical endocrinology and metabolism.

[245]  S. E. Harris,et al.  MEPE expression in osteocytes during orthodontic tooth movement. , 2007, Archives of oral biology.

[246]  S. Ashrafi,et al.  The Canalicular Structure of Compact Bone in the Rat at Different Ages , 2002, Microscopy and Microanalysis.

[247]  Xi Jiang,et al.  Neuropeptide Y is expressed by osteocytes and can inhibit osteoblastic activity , 2009, Journal of cellular biochemistry.

[248]  Daniel P Nicolella,et al.  Dendritic processes of osteocytes are mechanotransducers that induce the opening of hemichannels , 2010, Proceedings of the National Academy of Sciences.

[249]  A. van der Plas,et al.  Isolation and purification of osteocytes , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[250]  E. Kastritis,et al.  Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: Reduction post‐bortezomib monotherapy , 2012, International journal of cancer.

[251]  R. Suzuki,et al.  Some osteocytes released from their lacunae are embedded again in the bone and not engulfed by osteoclasts during bone remodeling , 2000, Anatomy and Embryology.

[252]  A. Robling,et al.  The Wnt Co-receptor LRP5 Is Essential for Skeletal Mechanotransduction but Not for the Anabolic Bone Response to Parathyroid Hormone Treatment* , 2006, Journal of Biological Chemistry.

[253]  S. Fernandez,et al.  Zoledronic acid decreases bone formation without causing osteocyte death in mice. , 2009, Archives of oral biology.

[254]  A. Parfitt,et al.  Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs. , 2005, American journal of physiology. Cell physiology.

[255]  A. E. El Haj,et al.  Hormonally-regulated expression of voltage-operated Ca(2+) channels in osteocytic (MLO-Y4) cells. , 2001, Biochemical and biophysical research communications.

[256]  E. Puscheck,et al.  Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[257]  Jenneke Klein-Nulend,et al.  Osteocytes subjected to pulsating fluid flow regulate osteoblast proliferation and differentiation. , 2006, Biochemical and biophysical research communications.

[258]  L. Bonewald,et al.  Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin. , 2005, Molecular biology of the cell.

[259]  S. Cowin,et al.  Ultrastructure of the osteocyte process and its pericellular matrix. , 2004, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[260]  E. B. Ruth Basophilic islands in osseous tissue and their relation to resorption , 1961, The Anatomical record.

[261]  D. Carnes,et al.  Surface plasmon resonance (SPR) confirms that MEPE binds to PHEX via the MEPE-ASARM motif: a model for impaired mineralization in X-linked rickets (HYP). , 2005, Bone.

[262]  Stephen E. Harris,et al.  E11/gp38 Selective Expression in Osteocytes: Regulation by Mechanical Strain and Role in Dendrite Elongation , 2006, Molecular and Cellular Biology.

[263]  C. Jacobs,et al.  Functional Gap Junctions Between Osteocytic and Osteoblastic Cells , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[264]  E. Farrow,et al.  Parathyroid hormone receptor signaling in osteocytes increases the expression of fibroblast growth factor-23 in vitro and in vivo. , 2011, Bone.

[265]  D B Kimmel,et al.  Prostaglandin E2 increases the skeletal response to mechanical loading. , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[266]  J. Aubin,et al.  Advances in the osteoblast lineage. , 1998, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[267]  A. Teti,et al.  Mature osteocytes behaviour in a repletion period: the occurrence of osteoplastic activity. , 1983, Basic and applied histochemistry.

[268]  M. Collins,et al.  Serum levels of matrix extracellular phosphoglycoprotein (MEPE) in normal humans correlate with serum phosphorus, parathyroid hormone and bone mineral density. , 2004, The Journal of clinical endocrinology and metabolism.

[269]  L. Bonewald,et al.  Mechanical Loading Stimulates Dentin Matrix Protein 1 (DMP1) Expression in Osteocytes In Vivo , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[270]  B. Katzenellenbogen,et al.  Nongenotropic, Sex-Nonspecific Signaling through the Estrogen or Androgen Receptors Dissociation from Transcriptional Activity , 2001, Cell.

[271]  E. Nunez,et al.  Activation of osteoclasts and the repopulation of bone surfaces following hibernation in the bat, Myotis lucifugus , 1985, The Anatomical record.

[272]  G. Loots,et al.  Parathyroid Hormone (PTH)–Induced Bone Gain Is Blunted in SOST Overexpressing and Deficient Mice , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[273]  J. Reeve,et al.  The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. , 1997, The Journal of clinical endocrinology and metabolism.

[274]  T. Bellido Antagonistic interplay between mechanical forces and glucocorticoids in bone: A tale of kinases , 2010, Journal of cellular biochemistry.

[275]  C. Palumbo A three-dimensional ultrastructural study of osteoid-osteocytes in the tibia of chick embryos , 2004, Cell and Tissue Research.

[276]  K. Hirokawa,et al.  Expression Profiles of Receptor Activator of Nuclear Factor κB Ligand, Receptor Activator of Nuclear Factor κB, and Osteoprotegerin Messenger RNA in Aged and Ovariectomized Rat Bones , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[277]  S. Ott Sclerostin and Wnt signaling--the pathway to bone strength. , 2005, The Journal of clinical endocrinology and metabolism.

[278]  C. Benhamou,et al.  Low bone accrual is associated with osteocyte apoptosis in alcohol-induced osteopenia. , 2011, Bone.

[279]  P. Niederer,et al.  In vivo tracer transport through the lacunocanalicular system of rat bone in an environment devoid of mechanical loading. , 1998, Bone.

[280]  A. Hedge,et al.  ASARM peptides: PHEX-dependent and -independent regulation of serum phosphate. , 2011, American journal of physiology. Renal physiology.

[281]  M. Balooch,et al.  Glucocorticoid‐Treated Mice Have Localized Changes in Trabecular Bone Material Properties and Osteocyte Lacunar Size That Are Not Observed in Placebo‐Treated or Estrogen‐Deficient Mice , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[282]  Stephen C Cowin,et al.  Estimation of bone permeability using accurate microstructural measurements. , 2006, Journal of biomechanics.

[283]  R. Suzuki,et al.  The reaction of osteoclasts when releasing osteocytes from osteocytic lacunae in the bone during bone modeling. , 2003, Tissue & cell.

[284]  N. Itoh,et al.  Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. , 2000, Biochemical and biophysical research communications.

[285]  L. Bonewald,et al.  Studying osteocyte function using the cell lines MLO-Y4 and MLO-A5. , 2012, Methods in molecular biology.

[286]  J. Robb,et al.  Electrophysiological Responses of Human Bone Cells to Mechanical Stimulation: Evidence for Specific Integrin Function in Mechanotransduction , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[287]  E. Katchburian,et al.  Electron microscopy of developing calvaria reveals images that suggest that osteoclasts engulf and destroy osteocytes during bone resorption , 1990, Calcified Tissue International.

[288]  M. Hamrick A Role for Myokines in Muscle-Bone Interactions , 2011, Exercise and sport sciences reviews.

[289]  D. Rao,et al.  Reduced Iliac Cancellous Osteocyte Density in Patients With Osteoporotic Vertebral Fracture , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[290]  P. Roberson,et al.  Osteoprotegerin prevents glucocorticoid-induced osteocyte apoptosis in mice. , 2011, Endocrinology.

[291]  C A Baud,et al.  Submicroscopic structure and functional aspects of the osteocyte. , 1968, Clinical orthopaedics and related research.

[292]  K. Michaëlsson,et al.  Circulating Fibroblast Growth Factor-23 Is Associated With Fat Mass and Dyslipidemia in Two Independent Cohorts of Elderly Individuals , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[293]  M. Forwood,et al.  Inducible cyclo‐oxygenase (COX‐2) mediates the induction of bone formation by mechanical loading in vivo , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[294]  L. Bonewald,et al.  Mechanism by which MLO-A5 Late Osteoblasts/Early Osteocytes Mineralize in Culture: Similarities with Mineralization of Lamellar Bone , 2006, Calcified Tissue International.

[295]  S. Kato,et al.  Inhibition of Intestinal Sodium‐dependent Inorganic Phosphate Transport by Fibroblast Growth Factor 23 , 2005, Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy.

[296]  L. Bonewald,et al.  Isolation and culture of primary osteocytes from the long bones of skeletally mature and aged mice. , 2012, BioTechniques.

[297]  A. Neri,et al.  Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation , 2012, Leukemia.

[298]  X. Guo,et al.  Osteocytic network is more responsive in calcium signaling than osteoblastic network under fluid flow , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[299]  H. Rauvala,et al.  Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading. , 2009, Bone.

[300]  Jie J. Zheng,et al.  The LRP5 High-Bone-Mass G171V Mutation Disrupts LRP5 Interaction with Mesd , 2004, Molecular and Cellular Biology.

[301]  E. Posvar,et al.  Single‐dose, placebo‐controlled, randomized study of AMG 785, a sclerostin monoclonal antibody , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[302]  J. Wergedal,et al.  DISTRIBUTION OF ACID AND ALKALINE PHOSPHATASE ACTIVITY IN UNDEMINERALIZED SECTIONS OF THE RAT TIBIAL DIAPHYSIS , 1969, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[303]  H. Jüppner,et al.  Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. , 2003, Kidney international.

[304]  Jian Q. Feng,et al.  Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[305]  K. Okawa,et al.  Klotho converts canonical FGF receptor into a specific receptor for FGF23 , 2006, Nature.

[306]  C. Halleux,et al.  Mef2c deletion in osteocytes results in increased bone mass , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[307]  D. Salter,et al.  CD44 expression in human bone: A novel marker of osteocytic differentiation , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[308]  A. Griffiths,et al.  Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease , 2007, Inflammatory bowel diseases.

[309]  A. E. El Haj,et al.  Three types of K(+) currents in murine osteocyte-like cells (MLO-Y4). , 2001, Bone.

[310]  Kosaku Kurata,et al.  Evidence for osteocyte regulation of bone homeostasis through RANKL expression , 2011, Nature Medicine.

[311]  L. Bonewald Osteocytes as Dynamic Multifunctional Cells , 2007, Annals of the New York Academy of Sciences.

[312]  Lynda F. Bonewald,et al.  CHAPTER 8 – Osteocytes , 2008 .

[313]  L. Bonewald,et al.  Dynamics of the transition from osteoblast to osteocyte , 2010, Annals of the New York Academy of Sciences.

[314]  Mark L. Johnson,et al.  Skeletal muscle secreted factors prevent glucocorticoid-induced osteocyte apoptosis through activation of β-catenin. , 2012, European cells & materials.

[315]  Xi Jiang,et al.  Pathogenic role of Fgf23 in Hyp mice. , 2006, American journal of physiology. Endocrinology and metabolism.

[316]  Hai Qing,et al.  Mechanical Induction of PGE2 in Osteocytes Blocks Glucocorticoid-Induced Apoptosis Through Both the β-Catenin and PKA Pathways , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[317]  Jinhu Xiong,et al.  Matrix-embedded cells control osteoclast formation , 2011, Nature Medicine.

[318]  T. Martin,et al.  Localization of RANKL (receptor activator of NF kappa B ligand) mRNA and protein in skeletal and extraskeletal tissues. , 1999, Bone.

[319]  Guoyin Feng,et al.  Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β‐Catenin Signaling , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.