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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Osteocytes


High impact information on Osteocytes

  • We show here that SOST/sclerostin is expressed exclusively by osteocytes in mouse and human bone and inhibits the differentiation and mineralization of murine preosteoblastic cells (KS483) [6].
  • Thus, failure of collagenase cleavage of type I collagen in Col1a1(r/r) mice is associated with osteocyte/osteoblast death but increases bone deposition in a manner that mimics the parathyroid hormone-induced bone surface activation seen in wild-type mice [7].
  • Osteocyte perilacunar matrices stained with Ab that recognizes collagenase collagen alpha1(I) chain cleavage ends in wild-type but not Col1a1(r/r) calvariae [7].
  • In hematoxylin and eosin-stained paraffin sections, we detect empty lacunae in osteocytes in calvariae from Col1a1(r/r) mice at age 2 weeks, increasing through age 10-12 months [7].
  • Glucocorticoid-induced osteoporosis may be due, in part, to increased apoptosis of osteocytes and osteoblasts, and bisphosphonates (BPs) are effective in the management of this condition [8].

Chemical compound and disease context of Osteocytes

  • The dead cell stain Ethidium homodimer-1 was used to tag dead osteocytes immediately after occlusion and produced a measure designated "osteonecrosis index." To detect leukocytes adhering to vessel walls, carboxyfluorescein diacetate, succinimidyl ester was injected at occluder release [9].
  • The release of bone calcium and the resulting hypercalcemia in vitamin D3 toxicosis is therefore due to a direct toxic effect of the vitamin, or its metabolites, on the osteocyte resulting in osteonecrosis [10].

Biological context of Osteocytes


Anatomical context of Osteocytes


Associations of Osteocytes with chemical compounds

  • These studies suggest that the EP2 receptor mediates the effects of autocrine PGE2 on the osteocyte gap junction in response to fluid flow-induced shear stress [19].
  • However,the pericellular space of some osteocytes in rats given 5 units of 1,25-(OH)2D3 contained electron-dense granular deposits that were interpreted to be calcium phosphate [20].
  • Cortisol at both dose levels failed to alter the electron microscopic appearance of osteoblasts, osteocytes, and osteoclasts with or without vitamin D. Bone turnover indicated by urinary hydroxyproline excretion was unaffected by cortisol treatment [21].
  • Nitric oxide is one of the signaling molecules that is released upon mechanical stimulation of osteocytes and osteoblasts [22].
  • Conversely, prolongation of ERK activation in osteocytes, by means of leptomycin B-induced inhibition of ERK export from the nucleus or overexpression of a green fluorescent protein-ERK2 mutant that resides permanently in the nucleus, converted the anti-apoptotic effect of 17beta-estradiol to a pro-apoptotic one [23].

Gene context of Osteocytes


Analytical, diagnostic and therapeutic context of Osteocytes

  • In situ hybridization studies were performed to examine the spatial and temporal expression patterns of Dmp1 during development in mouse embryos from 12.5 day postcoitus (dpc) to 8 weeks postnatal; these studies showed that Dmp1 first appeared in hypertrophic cartilage cells, followed by osteoblasts, and later was expressed strongly in osteocytes [29].
  • Therefore, in this study, we have used a rat model of ovariectomy (OVX) to determine whether the effect of estrogen withdrawal extends to other species and to clarify the role of estrogen in the maintenance of osteocyte viability [30].
  • In the current studies, expression of Bax, a proapoptotic gene product, and Bcl-2, an antiapoptotic gene product, was determined in osteocytes of fatigued rat bone using immunocytochemical staining and compared with TUNEL staining patterns [13].
  • Mechanical reloading of the hind limbs after 14 days of tail suspension caused a transient increase within 2 h of the expression of cyclooxygenase (COX)-2 in intraosseous cells, composed mainly of osteocytes, and in the expression of c-fos in periosteal cells [31].
  • A high dose of methylprednisolone was administered intramuscularly to rabbits, and we studied the accumulation of lipid in the osteocytes of the femoral head by histochemical methods and electron microscopy [32].


  1. Upregulation of osteopontin by osteocytes deprived of mechanical loading or oxygen. Gross, T.S., King, K.A., Rabaia, N.A., Pathare, P., Srinivasan, S. J. Bone Miner. Res. (2005) [Pubmed]
  2. Bone histomorphometric and biochemical marker results of a 2-year placebo-controlled trial of raloxifene in postmenopausal women. Ott, S.M., Oleksik, A., Lu, Y., Harper, K., Lips, P. J. Bone Miner. Res. (2002) [Pubmed]
  3. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. Weinstein, R.S., Nicholas, R.W., Manolagas, S.C. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  4. An electron microscopic study of the changes observed in osteocytes under ischemic conditions. Usui, Y., Kawai, K., Hirohata, K. J. Orthop. Res. (1989) [Pubmed]
  5. Osteocytes inhibit osteoclastic bone resorption through transforming growth factor-beta: enhancement by estrogen. Heino, T.J., Hentunen, T.A., Väänänen, H.K. J. Cell. Biochem. (2002) [Pubmed]
  6. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. van Bezooijen, R.L., Roelen, B.A., Visser, A., van der Wee-Pals, L., de Wilt, E., Karperien, M., Hamersma, H., Papapoulos, S.E., ten Dijke, P., Löwik, C.W. J. Exp. Med. (2004) [Pubmed]
  7. Osteocyte and osteoblast apoptosis and excessive bone deposition accompany failure of collagenase cleavage of collagen. Zhao, W., Byrne, M.H., Wang, Y., Krane, S.M. J. Clin. Invest. (2000) [Pubmed]
  8. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. Plotkin, L.I., Weinstein, R.S., Parfitt, A.M., Roberson, P.K., Manolagas, S.C., Bellido, T. J. Clin. Invest. (1999) [Pubmed]
  9. Model for intravital microscopic evaluation of the effects of arterial occlusion-caused ischemia in bone. Hsieh, A.S., Winet, H., Bao, J.Y., Stevanovic, M. Annals of biomedical engineering. (1999) [Pubmed]
  10. Vitamin D toxicity. Initial site and mode of action. Haschek, W.M., Krook, L., Kallfelz, F.A., Pond, W.G. The Cornell veterinarian. (1978) [Pubmed]
  11. Estrogen suppresses activation but enhances formation phase of osteogenic response to mechanical stimulation in rat bone. Jagger, C.J., Chow, J.W., Chambers, T.J. J. Clin. Invest. (1996) [Pubmed]
  12. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. Winkler, D.G., Sutherland, M.K., Geoghegan, J.C., Yu, C., Hayes, T., Skonier, J.E., Shpektor, D., Jonas, M., Kovacevich, B.R., Staehling-Hampton, K., Appleby, M., Brunkow, M.E., Latham, J.A. EMBO J. (2003) [Pubmed]
  13. Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation? Verborgt, O., Tatton, N.A., Majeska, R.J., Schaffler, M.B. J. Bone Miner. Res. (2002) [Pubmed]
  14. Distinct anabolic response of osteoblast to low-intensity pulsed ultrasound. Naruse, K., Miyauchi, A., Itoman, M., Mikuni-Takagaki, Y. J. Bone Miner. Res. (2003) [Pubmed]
  15. In situ measurement of solute transport in the bone lacunar-canalicular system. Wang, L., Wang, Y., Han, Y., Henderson, S.C., Majeska, R.J., Weinbaum, S., Schaffler, M.B. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  16. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Campagnoli, C., Roberts, I.A., Kumar, S., Bennett, P.R., Bellantuono, I., Fisk, N.M. Blood (2001) [Pubmed]
  17. Targeted disruption of the lysosomal alpha-mannosidase gene results in mice resembling a mild form of human alpha-mannosidosis. Stinchi, S., Lüllmann-Rauch, R., Hartmann, D., Coenen, R., Beccari, T., Orlacchio, A., von Figura, K., Saftig, P. Hum. Mol. Genet. (1999) [Pubmed]
  18. Interaction of dichloromethylene diphosphonate and vitamin D on bone of thyroparathyroidectomized rats. Weisbrode, S.E., Capen, C.C., Pendley, C.B. Am. J. Pathol. (1977) [Pubmed]
  19. Effects of mechanical strain on the function of Gap junctions in osteocytes are mediated through the prostaglandin EP2 receptor. Cherian, P.P., Cheng, B., Gu, S., Sprague, E., Bonewald, L.F., Jiang, J.X. J. Biol. Chem. (2003) [Pubmed]
  20. Ultrastructural evaluation of the effects of 1,25-dihydroxyvitamin D3 on bone of thyroparathyroidectomized rats fed a low-calcium diet. Weisbrode, S.E., Capen, C.C., Norman, A.W. Am. J. Pathol. (1978) [Pubmed]
  21. Ultrastructural evaluation of the interaction of glucocorticoids and vitamin D on bone cells in thyroparathyroidectomized rats. Weisbrode, S.E., Capen, C.C. Am. J. Pathol. (1976) [Pubmed]
  22. Expression of serotonin receptors in bone. Westbroek, I., van der Plas, A., de Rooij, K.E., Klein-Nulend, J., Nijweide, P.J. J. Biol. Chem. (2001) [Pubmed]
  23. Transient versus sustained phosphorylation and nuclear accumulation of ERKs underlie anti-versus pro-apoptotic effects of estrogens. Chen, J.R., Plotkin, L.I., Aguirre, J.I., Han, L., Jilka, R.L., Kousteni, S., Bellido, T., Manolagas, S.C. J. Biol. Chem. (2005) [Pubmed]
  24. Dentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo. Yang, W., Lu, Y., Kalajzic, I., Guo, D., Harris, M.A., Gluhak-Heinrich, J., Kotha, S., Bonewald, L.F., Feng, J.Q., Rowe, D.W., Turner, C.H., Robling, A.G., Harris, S.E. J. Biol. Chem. (2005) [Pubmed]
  25. Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype. Thomas, G., Moffatt, P., Salois, P., Gaumond, M.H., Gingras, R., Godin, E., Miao, D., Goltzman, D., Lanctôt, C. J. Biol. Chem. (2003) [Pubmed]
  26. Mechanical loading stimulates dentin matrix protein 1 (DMP1) expression in osteocytes in vivo. Gluhak-Heinrich, J., Ye, L., Bonewald, L.F., Feng, J.Q., MacDougall, M., Harris, S.E., Pavlin, D. J. Bone Miner. Res. (2003) [Pubmed]
  27. Ontogeny of Phex/PHEX protein expression in mouse embryo and subcellular localization in osteoblasts. Thompson, D.L., Sabbagh, Y., Tenenhouse, H.S., Roche, P.C., Drezner, M.K., Salisbury, J.L., Grande, J.P., Poeschla, E.M., Kumar, R. J. Bone Miner. Res. (2002) [Pubmed]
  28. Early strain-related changes in enzyme activity in osteocytes following bone loading in vivo. Skerry, T.M., Bitensky, L., Chayen, J., Lanyon, L.E. J. Bone Miner. Res. (1989) [Pubmed]
  29. Dentin matrix protein 1, a target molecule for Cbfa1 in bone, is a unique bone marker gene. Fen, J.Q., Zhang, J., Dallas, S.L., Lu, Y., Chen, S., Tan, X., Owen, M., Harris, S.E., MacDougall, M. J. Bone Miner. Res. (2002) [Pubmed]
  30. The role of estrogen in the control of rat osteocyte apoptosis. Tomkinson, A., Gevers, E.F., Wit, J.M., Reeve, J., Noble, B.S. J. Bone Miner. Res. (1998) [Pubmed]
  31. Effect of mechanical unloading and reloading on periosteal bone formation and gene expression in tail-suspended rapidly growing rats. Matsumoto, T., Nakayama, K., Kodama, Y., Fuse, H., Nakamura, T., Fukumoto, S. Bone (1998) [Pubmed]
  32. Steroid-induced accumulation of lipid in the osteocytes of the rabbit femoral head. A histochemical and electron microscopic study. Kawai, K., Tamaki, A., Hirohata, K. The Journal of bone and joint surgery. American volume. (1985) [Pubmed]
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