Bone remodelling at a glance

The bone remodelling cycle (see Poster panel “The bone remodelling cycle”) maintains the integrity of the skeleton through the balanced activities of its constituent cell types. These are the bone-forming osteoblast, a cell that produces the organic bone matrix and aids its mineralisation ([

[1]  R. Civitelli Cell-cell communication in the osteoblast/osteocyte lineage. , 2008, Archives of biochemistry and biophysics.

[2]  Jacques P. Brown,et al.  The p62 P392L mutation linked to Paget's disease induces activation of human osteoclasts. , 2009, Molecular endocrinology.

[3]  E. Bradley,et al.  Novel Pro-survival Functions of the Kruppel-like Transcription Factor Egr2 in Promotion of Macrophage Colony-stimulating Factor-mediated Osteoclast Survival Downstream of the MEK/ERK Pathway* , 2008, Journal of Biological Chemistry.

[4]  Richard P Lifton,et al.  High bone density due to a mutation in LDL-receptor-related protein 5. , 2002, The New England journal of medicine.

[5]  S. Santavirta,et al.  Recombinant Human Bone Morphogenetic Protein-2 for Treatment of Open Tibial Fractures: A Prospective, Controlled, Randomized Study of Four Hundred and Fifty Patients , 2002, The Journal of bone and joint surgery. American volume.

[6]  Y. Kadono,et al.  Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3‐only Bcl‐2 family member Bim , 2003, The EMBO journal.

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

[8]  L. Addadi,et al.  The Architecture of the Adhesive Apparatus of Cultured Osteoclasts: From Podosome Formation to Sealing Zone Assembly , 2007, PloS one.

[9]  J. John Mann,et al.  Lrp5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum , 2008, Cell.

[10]  H. Väänänen,et al.  Intracellular membrane trafficking in bone resorbing osteoclasts , 2003, Microscopy research and technique.

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

[12]  C. Ackert-Bicknell,et al.  Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. , 2009, Critical reviews in eukaryotic gene expression.

[13]  C. Jacobs,et al.  β1 Integrins Mediate Mechanosensitive Signaling Pathways in Osteocytes , 2010, Calcified Tissue International.

[14]  R. Baron,et al.  Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation. , 2010, Cell metabolism.

[15]  Kenji F. Tanaka,et al.  A Serotonin-Dependent Mechanism Explains the Leptin Regulation of Bone Mass, Appetite, and Energy Expenditure , 2009, Cell.

[16]  David Mellis,et al.  Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. , 2008, American journal of human genetics.

[17]  Christopher R Jacobs,et al.  Osteocyte mechanobiology and pericellular mechanics. , 2010, Annual review of biomedical engineering.

[18]  Joseph A. Mindell,et al.  The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes , 2008, Nature.

[19]  H. Väänänen,et al.  Endocytic pathway from the basal plasma membrane to the ruffled border membrane in bone-resorbing osteoclasts. , 1997, Journal of cell science.

[20]  D. Kimmel,et al.  Generation and Selection of Novel Fully Human Monoclonal Antibodies That Neutralize Dickkopf-1 (DKK1) Inhibitory Function in Vitro and Increase Bone Mass in Vivo , 2010, The Journal of Biological Chemistry.

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

[22]  J. Carroll,et al.  Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival , 2008, The EMBO journal.

[23]  P. Saftig,et al.  The Bone Lining Cell: Its Role in Cleaning Howship's Lacunae and Initiating Bone Formation , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  J. Bidwell,et al.  Fluid Shear Stress Induces β-Catenin Signaling in Osteoblasts , 2004, Calcified Tissue International.

[25]  A. Schulz,et al.  Loss of the ClC-7 Chloride Channel Leads to Osteopetrosis in Mice and Man , 2001, Cell.

[26]  J. Crockett,et al.  New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis , 2010, Osteoporosis International.

[27]  S. Weinbaum,et al.  Attachment of Osteocyte Cell Processes to the Bone Matrix , 2009, Anatomical record.

[28]  N. Bishop,et al.  Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL , 2007, Nature Genetics.

[29]  S. Weinbaum,et al.  A model for the role of integrins in flow induced mechanotransduction in osteocytes , 2007, Proceedings of the National Academy of Sciences.

[30]  Yurii S. Aulchenko,et al.  Twenty bone mineral density loci identified by large-scale meta-analysis of genome-wide association studies , 2009, Nature Genetics.

[31]  Richard M Aspden,et al.  Parallel-plate fluid flow systems for bone cell stimulation. , 2010, Journal of biomechanics.

[32]  M. Horton,et al.  Beta 1 integrins and osteoclast function: involvement in collagen recognition and bone resorption. , 1996, Bone.

[33]  S. Hardy,et al.  Impaired bone formation in transgenic mice resulting from altered integrin function in osteoblasts. , 2000, Developmental biology.

[34]  R. Pacifici,et al.  T Cells: Unexpected Players in the Bone Loss Induced by Estrogen Deficiency and in Basal Bone Homeostasis , 2007, Annals of the New York Academy of Sciences.

[35]  L. Lanier,et al.  Role of ITAM‐containing adapter proteins and their receptors in the immune system and bone , 2005, Immunological reviews.

[36]  T. Jentsch,et al.  ClC-7 requires Ostm1 as a β-subunit to support bone resorption and lysosomal function , 2006, Nature.

[37]  M. Rogers,et al.  Recent advances in understanding the mechanism of action of bisphosphonates. , 2006, Current opinion in pharmacology.

[38]  K. Kaestner,et al.  The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity , 2008, The Journal of cell biology.

[39]  C. L. Benhamou,et al.  Osteocyte: the unrecognized side of bone tissue , 2010, Osteoporosis International.

[40]  Masaki Noda,et al.  Leptin regulation of bone resorption by the sympathetic nervous system and CART , 2005, Nature.

[41]  J. A. Robinson,et al.  High Bone Mass in Mice Expressing a Mutant LRP5 Gene , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[42]  J. Bidwell,et al.  Fluid shear stress induces beta-catenin signaling in osteoblasts. , 2004, Calcified tissue international.

[43]  S. Nesbitt,et al.  β1 integrins and osteoclast function: Involvement in collagen recognition and bone resorption , 1996 .

[44]  S. Teitelbaum Osteoclasts: what do they do and how do they do it? , 2007, The American journal of pathology.

[45]  V. Everts,et al.  Osteoclast heterogeneity: lessons from osteopetrosis and inflammatory conditions. , 2009, Biochimica et biophysica acta.

[46]  K. Matsuo Eph and ephrin interactions in bone. , 2010, Advances in experimental medicine and biology.

[47]  A. Pitsillides,et al.  Osteocytes use estrogen receptor alpha to respond to strain but their ERalpha content is regulated by estrogen. , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[48]  M. Karsdal,et al.  The role of chloride channels in osteoclasts: ClC-7 as a target for osteoporosis treatment. , 2005, Drug news & perspectives.

[49]  G. Karsenty,et al.  Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation , 1997, Cell.

[50]  G. Stenbeck Formation and function of the ruffled border in osteoclasts. , 2002, Seminars in cell & developmental biology.

[51]  T. Jentsch,et al.  ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function , 2007 .

[52]  M. Rogers,et al.  RANKL increases the level of Mcl-1 in osteoclasts and reduces bisphosphonate-induced osteoclast apoptosis in vitro , 2009, Arthritis research & therapy.

[53]  Jenneke Klein-Nulend,et al.  Early activation of the beta-catenin pathway in osteocytes is mediated by nitric oxide, phosphatidyl inositol-3 kinase/Akt, and focal adhesion kinase. , 2010, Biochemical and biophysical research communications.

[54]  Di Chen,et al.  The BMP signaling and in vivo bone formation. , 2005, Gene.

[55]  W. Hul,et al.  Identification of the disease-causing gene in sclerosteosis--discovery of a novel bone anabolic target? , 2004, Journal of musculoskeletal & neuronal interactions.

[56]  T. Steinberg,et al.  Intercellular Junctions and Cell-Cell Communication in Bone , 2002 .

[57]  T. Tanaka,et al.  Study of immunoelectron microscopic localization of cathepsin K in osteoclasts and other bone cells in the mouse femur. , 1998, Bone.

[58]  R. Talmage,et al.  Removal of calcium from bone as influenced by the parathyroids. , 1958, Endocrinology.

[59]  O. Verborgt,et al.  Osteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[60]  Chao Wan,et al.  Insulin Receptor Signaling in Osteoblasts Regulates Postnatal Bone Acquisition and Body Composition , 2010, Cell.

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

[62]  Xizhi Guo,et al.  Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. , 2005, Developmental cell.

[63]  T. Plesner,et al.  A physical mechanism for coupling bone resorption and formation in adult human bone. , 2008, The American journal of pathology.

[64]  P. Marie Role of N‐cadherin in bone formation , 2002, Journal of cellular physiology.

[65]  M. McKee,et al.  Endocrine Regulation of Energy Metabolism by the Skeleton , 2007, Cell.

[66]  A. Villa,et al.  Infantile Malignant, Autosomal Recessive Osteopetrosis: The Rich and The Poor , 2008, Calcified Tissue International.

[67]  P. Lehenkari,et al.  Removal of osteoclast bone resorption products by transcytosis. , 1997, Science.

[68]  L. Xing,et al.  Regulation of apoptosis in osteoclasts and osteoblastic cells. , 2005, Biochemical and biophysical research communications.

[69]  F. Coxon,et al.  Vesicular trafficking in osteoclasts. , 2008, Seminars in cell & developmental biology.

[70]  Hans Clevers,et al.  Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. , 2005, Developmental cell.

[71]  Qing Chen,et al.  Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[72]  F. Saltel,et al.  Apatite-mediated actin dynamics in resorbing osteoclasts. , 2004, Molecular biology of the cell.

[73]  T. Martin,et al.  Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice. , 2010, The Journal of clinical investigation.

[74]  H. Wieczorek,et al.  Inhibitors of V-ATPases: old and new players , 2009, Journal of Experimental Biology.

[75]  R. Faccio,et al.  Osteoclast motility: Putting the brakes on bone resorption , 2011, Ageing Research Reviews.

[76]  Josée Dupuis,et al.  Genome-wide association with bone mass and geometry in the Framingham Heart Study , 2007, BMC Medical Genetics.

[77]  G. Karsenty,et al.  Genetic control of bone formation. , 2009, Annual review of cell and developmental biology.

[78]  J. Penninger,et al.  RANK/RANKL: Regulators of Immune Responses and Bone Physiology , 2008, Annals of the New York Academy of Sciences.

[79]  S. Harris,et al.  Bone Morphogenetic Protein 2 (BMP-2) Enhances BMP-3, BMP-4, and Bone Cell Differentiation Marker Gene Expression During the Induction of Mineralized Bone Matrix Formation in Culturesof Fetal Rat Calvarial Osteoblasts , 1997, Calcified Tissue International.

[80]  M. Zaidi,et al.  Forty years of calcitonin--where are we now? A tribute to the work of Iain Macintyre, FRS. , 2002, Bone.

[81]  Claus Christiansen,et al.  Are Nonresorbing Osteoclasts Sources of Bone Anabolic Activity? , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[82]  N. Sims,et al.  Cardiotrophin‐1 Is an Osteoclast‐Derived Stimulus of Bone Formation Required for Normal Bone Remodeling , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[83]  C. Rabourdin-Combe,et al.  Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment. , 2004, Blood.

[84]  K. Hultenby,et al.  Proteolytic Excision of a Repressive Loop Domain in Tartrate-resistant Acid Phosphatase by Cathepsin K in Osteoclasts* , 2005, Journal of Biological Chemistry.

[85]  Mark L. Johnson,et al.  A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. , 2002, American journal of human genetics.

[86]  C. Czupalla,et al.  Src-dependent repression of ARF6 is required to maintain podosome-rich sealing zones in bone-digesting osteoclasts , 2009, Proceedings of the National Academy of Sciences.

[87]  S. Nesbitt,et al.  Rat osteoclasts adhere to a wide range of rgd (arg‐gly‐asp) peptide‐containing proteins, including the bone sialoproteins and fibronectin, via a β3 integrin , 1992 .

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

[89]  J. Aubin Bone formation : maturation and functional activities of osteoblast lineage cells , 2006 .

[90]  P. Chambon,et al.  Estrogen Prevents Bone Loss via Estrogen Receptor α and Induction of Fas Ligand in Osteoclasts , 2007, Cell.

[91]  M. Horton,et al.  Vitronectin receptor has a role in bone resorption but does not mediate tight sealing zone attachment of osteoclasts to the bone surface , 1991, The Journal of cell biology.

[92]  V. Parikka,et al.  Downregulation of Small GTPase Rab7 Impairs Osteoclast Polarization and Bone Resorption* 210 , 2001, The Journal of Biological Chemistry.

[93]  A. Parfitt,et al.  What old means to bone , 2010, Trends in Endocrinology & Metabolism.

[94]  P. Chambon,et al.  Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. , 2007, Cell.

[95]  M. Horton,et al.  Trafficking of matrix collagens through bone-resorbing osteoclasts. , 1997, Science.

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

[97]  R. Civitelli,et al.  Perspective: Cell–Cell Adhesion and Signaling Through Cadherins: Connecting Bone Cells in Their Microenvironment , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[98]  C. Turner,et al.  Sclerostin: A gem from the genome leads to bone‐building antibodies , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[99]  Chenbei Chang,et al.  Parathyroid hormone signaling through low-density lipoprotein-related protein 6. , 2008, Genes & development.

[100]  R. Jahn,et al.  Rab3D Regulates a Novel Vesicular Trafficking Pathway That Is Required for Osteoclastic Bone Resorption , 2005, Molecular and Cellular Biology.

[101]  R. DePinho,et al.  Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism , 2010, Cell.

[102]  D. D. de Luis,et al.  Odanacatib, a New Drug for the Treatment of Osteoporosis: Review of the Results in Postmenopausal Women , 2010, Journal of osteoporosis.

[103]  J. Weisel,et al.  Endocrine functions of bone in mineral metabolism regulation. , 2008, The Journal of clinical investigation.

[104]  J. Salo,et al.  Bone-resorbing osteoclasts reveal a dynamic division of basal plasma membrane into two different domains. , 1996, Journal of cell science.

[105]  T. Martin,et al.  Communication between ephrinB2 and EphB4 within the osteoblast lineage. , 2010, Advances in experimental medicine and biology.

[106]  E. Génot,et al.  CD44 and beta3 integrin organize two functionally distinct actin-based domains in osteoclasts. , 2007, Molecular biology of the cell.