Osteocyte and bone structure

The osteocyte is the most abundant cell type of bone. There are approximately 10 times as many osteocytes as osteoblasts in adult human bone, and the number of osteoclasts is only a fraction of the number of osteoblasts. Our current knowledge of the role of osteocytes in bone metabolism is far behind our insight into the properties and functions of the osteoblasts and osteoclasts. However, the striking structural design of bone predicts an important role for osteocytes in determining bone structure. Over the past several years, the role of osteocytes as the professional mechanosensory cells of bone, and the lacunocanalicular porosity as the structure that mediates mechanosensing have become clear. Strain-derived flow of interstitial fluid through this porosity seems to mechanically activate the osteocytes, as well as ensure transport of cell signaling molecules, nutrients, and waste products. This concept explains local bone gain and loss—as well as remodeling in response to fatigue damage—as processes supervised by mechanosensitive osteocytes. Alignment during remodeling seems to occur as a result of the osteocyte’s sensing different canalicular flow patterns around the cutting cone and reversal zone during loading, therefore determining the bone’s structure.

[1]  A. Pitsillides,et al.  Mechanical strain‐induced NO production by bone cells: a possible role in adaptive bone (re)modeling? , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  E H Burger,et al.  Differential stimulation of prostaglandin G/H synthase-2 in osteocytes and other osteogenic cells by pulsating fluid flow. , 2000, Biochemical and biophysical research communications.

[3]  C. Reutelingsperger,et al.  Phagocytosis of dying chondrocytes by osteoclasts in the mouse growth plate as demonstrated by annexin-V labelling , 2000, Cell and Tissue Research.

[4]  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.

[5]  E H Burger,et al.  Pulsating fluid flow increases prostaglandin production by cultured chicken osteocytes--a cytoskeleton-dependent process. , 1996, Biochemical and biophysical research communications.

[6]  L E Lanyon,et al.  Loading‐related increases in prostaglandin production in cores of adult canine cancellous bone in vitro: A role for prostacyclin in adaptive bone remodeling? , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

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

[8]  Rik Huiskes,et al.  Effects of mechanical forces on maintenance and adaptation of form in trabecular bone , 2000, Nature.

[9]  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.

[10]  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.

[11]  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.

[12]  A. Zeiher,et al.  Nitric oxide and apoptosis: another paradigm for the double-edged role of nitric oxide. , 1997, Nitric oxide : biology and chemistry.

[13]  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.

[14]  R. Dillaman Movement of ferritin in the 2‐day‐old chick femur , 1984, The Anatomical record.

[15]  S. Cowin,et al.  Candidates for the mechanosensory system in bone. , 1991, Journal of biomechanical engineering.

[16]  L. Lanyon,et al.  Cellular responses to mechanical loading in vitro , 1990, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  P. Nijweide,et al.  Identification of osteocytes in osteoblast-like cell cultures using a monoclonal antibody specifically directed against osteocytes , 2004, Histochemistry.

[18]  J. Klein-Nulend,et al.  MECHANOTRANSDUCTION IN BONE : ROLE OF THE LACUNOCANALICULAR NETWORK , 1999 .

[19]  E H Burger,et al.  Pulsating Fluid Flow Stimulates Prostaglandin Release and Inducible Prostaglandin G/H Synthase mRNA Expression in Primary Mouse Bone Cells , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[20]  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.

[21]  L. Lanyon,et al.  Regulation of bone formation by applied dynamic loads. , 1984, The Journal of bone and joint surgery. American volume.

[22]  R. Huiskes,et al.  Proposal for the regulatory mechanism of Wolff's law , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  J. A. Baart,et al.  Donor Age and Mechanosensitivity of Human Bone Cells , 2002, Osteoporosis International.

[24]  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.

[25]  G. Rodan,et al.  Indomethacin inhibition of tenotomy‐induced bone resorption in rats , 1988, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[26]  D. Ingber,et al.  Mechanotransduction across the cell surface and through the cytoskeleton , 1993 .

[27]  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.

[28]  S. Cowin,et al.  A case for bone canaliculi as the anatomical site of strain generated potentials. , 1995, Journal of biomechanics.

[29]  H. Datta,et al.  Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[30]  P. Lips,et al.  Response of normal and osteoporotic human bone cells to mechanical stress in vitro. , 1998, American journal of physiology. Endocrinology and metabolism.

[31]  Subrata Saha,et al.  A theoretical model for stress-generated fluid flow in the canaliculi-lacunae network in bone tissue. , 1990, Journal of biomechanics.

[32]  A. Zeiher,et al.  Nitric Oxide Down-regulates MKP-3 mRNA Levels , 2000, The Journal of Biological Chemistry.

[33]  K. Piekarski,et al.  Transport mechanism operating between blood supply and osteocytes in long bones , 1977, Nature.

[34]  R. Busse,et al.  Pulsatile Stretch and Shear Stress: Physical Stimuli Determining the Production of Endothelium-Derived Relaxing Factors , 1998, Journal of Vascular Research.

[35]  F. Glorieux,et al.  In vivo osteogenic activity of isolated human bone cells , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[36]  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.

[37]  N Loveridge,et al.  Identification of apoptotic changes in osteocytes in normal and pathological human bone. , 1997, Bone.

[38]  J. Chow,et al.  Increased insulin-like growth factor I mRNA expression in rat osteocytes in response to mechanical stimulation. , 1995, The American journal of physiology.

[39]  Theo H Smit,et al.  A Case for Strain‐Induced Fluid Flow as a Regulator of BMU‐Coupling and Osteonal Alignment , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[40]  A. van der Plas,et al.  Expression of Serotonin Receptors in Bone* , 2001, The Journal of Biological Chemistry.

[41]  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.

[42]  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.

[43]  Theo H Smit,et al.  Strain-derived canalicular fluid flow regulates osteoclast activity in a remodelling osteon--a proposal. , 2003, Journal of biomechanics.

[44]  T. Smit,et al.  Is BMU‐Coupling a Strain‐Regulated Phenomenon? A Finite Element Analysis , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[45]  L. Lanyon,et al.  Early strain‐related changes in enzyme activity in osteocytes following bone loading in vivo , 1989, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[46]  P. A. Watson,et al.  Function follows form: generation of intracellular signals by cell deformation , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[47]  E H Burger,et al.  Nitric oxide response to shear stress by human bone cell cultures is endothelial nitric oxide synthase dependent. , 1998, Biochemical and biophysical research communications.