Calcified Tissue International

, Volume 94, Issue 1, pp 25–34 | Cite as

Osteocyte-Driven Bone Remodeling

  • Teresita Bellido


Osteocytes, the most abundant cells in bone, have been long postulated to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts. The discovery that the inhibitor of bone formation sclerostin is primarily expressed in osteocytes in bone and downregulated by anabolic stimuli provided a mechanism by which osteocytes influence the activity of osteoblasts. Advances of the last few years provided experimental evidence demonstrating that osteocytes also participate in the recruitment of osteoclasts and the initiation of bone remodeling. Apoptotic osteocytes trigger yet-to-be-identified signals that attract osteoclast precursors to specific areas of bone, which in turn differentiate to mature, bone-resorbing osteoclasts. Osteocytes are also the source of molecules that regulate the generation and activity of osteoclasts, such as OPG and RANKL; and genetic manipulations of the mouse genome leading to loss or gain of function or to altered expression of either molecule in osteocytes markedly affect bone resorption. This review highlights these investigations and discusses how the novel concept of osteocyte-driven bone resorption and formation impacts our understanding of the mechanisms by which current therapies control bone remodeling.


Osteocyte Osteoclast Osteoblast Bone remodeling RANKL OPG Sost 



This research was supported by the National Institutes of Health (R01-AR053643, KO2-AR02127, R03 TW006919, R01-DK076007, and P01-AG13918).




  1. 1.
    Zhang K, Barragan-Adjemian C, Ye L, Kotha S, Dallas M, Lu Y, Zhao S et al (2006) E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation. Mol Cell Biol 26:4539–4552PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Holmbeck K, Bianco P, Caterina J, Yamada S, Kromer M, Kuznetsov SA, Mankani M et al (1999) MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99:81–92PubMedCrossRefGoogle Scholar
  3. 3.
    Holmbeck K, Bianco P, Pidoux I, Inoue S, Billinghurst RC, Wu W, Chrysovergis K et al (2005) The metalloproteinase MT1-MMP is required for normal development and maintenance of osteocyte processes in bone. J Cell Sci 118:147–156PubMedCrossRefGoogle Scholar
  4. 4.
    Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104:439–446PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Boyce BF, Xing L, Jilka RL, Bellido T, Weinstein RS, Parfitt AM, Manolagas SC (2002) Apoptosis in bone cells. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology. Academic Press, San Diego, pp 151–168CrossRefGoogle Scholar
  6. 6.
    Paic F, Igwe JC, Nori R, Kronenberg MS, Franceschetti T, Harrington P, Kuo L et al (2009) Identification of differentially expressed genes between osteoblasts and osteocytes. Bone 45:682–692PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Igwe JC, Gao Q, Kizivat T, Kao WW, Kalajzic I (2011) Keratocan is expressed by osteoblasts and can modulate osteogenic differentiation. Connect Tissue Res 52:401–407PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Benson MD, Aubin JE, Xiao G, Thomas PE, Franceschi RT (1999) Cloning of a 2.5 kb murine bone sialoprotein promoter fragment and functional analysis of putative Osf2 binding sites. J Bone Miner Res 14:396–405PubMedCrossRefGoogle Scholar
  9. 9.
    Kramer I, Halleux C, Keller H, Pegurri M, Gooi JH, Weber PB, Feng JQ et al (2010) Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol Cell Biol 30:3071–3085PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Bonewald LF (2011) The amazing osteocyte. J Bone Miner Res 26:229–238PubMedCrossRefGoogle Scholar
  11. 11.
    Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O’Brien CA, Manolagas SC et al (2005) Chronic elevation of PTH in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 146:4577–4583PubMedCrossRefGoogle Scholar
  12. 12.
    Wang L, Ciani C, Doty SB, Fritton SP (2004) Delineating bone’s interstitial fluid pathway in vivo. Bone 34:499–509PubMedCrossRefGoogle Scholar
  13. 13.
    Poole KE, Van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Lowik CW, Reeve J (2005) Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 19:1842–1844PubMedGoogle Scholar
  14. 14.
    Van Bezooijen RL, Roelen BA, Visser A, Wee-Pals L, de Wilt E, Karperien M, Hamersma H et al (2004) Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med 199:805–814PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D et al (2003) Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 22:6267–6276PubMedCrossRefGoogle Scholar
  16. 16.
    Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C et al (2001) Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10:537–543PubMedCrossRefGoogle Scholar
  17. 17.
    Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE et al (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577–589PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, D’Agostin D, Kurahara C et al (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23:860–869PubMedCrossRefGoogle Scholar
  19. 19.
    Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, Li Y et al (2009) Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res 24:1651–1661PubMedCrossRefGoogle Scholar
  20. 20.
    Loots GG, Kneissel M, Keller H, Baptist M, Chang J, Collette NM, Ovcharenko D et al (2005) Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res 15:928–935PubMedCrossRefGoogle Scholar
  21. 21.
    Rhee Y, Allen MR, Condon K, Lezcano V, Ronda AC, Galli C, Olivos N et al (2011) PTH receptor signaling in osteocytes governs periosteal bone formation and intra-cortical remodeling. J Bone Miner Res 26:1035–1046PubMedCrossRefGoogle Scholar
  22. 22.
    Warmington K, Morony S, Sarosi I, Gong G, Stepphens P, Winkler DG, Sutherland MK et al (2004) Sclerostin antagonism in adult rodents, via monoclonal antibody mediated blockade, increases bone mineral density and implicates sclerostin as a key regulator of bone mass during adulthood. J Bone Miner Res 19:S56Google Scholar
  23. 23.
    Warmington K, Ominsky M, Bolon B, Cattley R, Stephens P, Lawson A, Lightwood D et al (2005) Sclerostin monoclonal antibody treatment of osteoporotic rats completely reverses one year of ovariectomy-induced systemic bone loss. J Bone Miner Res 20:S22Google Scholar
  24. 24.
    Paszty C, Turner CH, Robinson MK (2010) Sclerostin: a gem from the genome leads to bone-building antibodies. J Bone Miner Res 25:1897–1904PubMedCrossRefGoogle Scholar
  25. 25.
    Jilka RL (2009) Inhibiting the inhibitor: a new route to bone anabolism. J Bone Miner Res 24:575–577PubMedCrossRefGoogle Scholar
  26. 26.
    Keller H, Kneissel M (2005) SOST is a target gene for PTH in bone. Bone 37:148–158PubMedCrossRefGoogle Scholar
  27. 27.
    van Lierop AH, Witteveen J, Hamdy N, Papapoulos S (2010) Patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls. Eur J Endocrinol 163:833–837PubMedCrossRefGoogle Scholar
  28. 28.
    Drake MT, Srinivasan B, Modder UI, Peterson JM, McCready LK, Riggs BL, Dwyer D et al (2010) Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. J Clin Endocrinol Metab 95:5056–5062PubMedCrossRefGoogle Scholar
  29. 29.
    Mirza FS, Padhi ID, Raisz LG, Lorenzo JA (2010) Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 95:1991–1997PubMedCrossRefGoogle Scholar
  30. 30.
    Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MJ, Alam I, Mantila SM et al (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem 283:5866–5875PubMedCrossRefGoogle Scholar
  31. 31.
    Tu X, Rhee Y, Condon KW, Bivi N, Allen MR, Dwyer D, Stolina M et al (2012) Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone 50:209–217PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-hora M, Feng JQ, Bonewald LF et al (2011) Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med 17:1231–1234PubMedCrossRefGoogle Scholar
  33. 33.
    Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O’Brien CA (2011) Matrix-embedded cells control osteoclast formation. Nat Med 17:1235–1241PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Aguirre JI, Plotkin LI, Stewart SA, Weinstein RS, Parfitt AM, Manolagas SC, Bellido T (2006) Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res 21:605–615PubMedCrossRefGoogle Scholar
  35. 35.
    Honma M, Ikebuchi Y, Kariya Y, Hayashi M, Hayashi N, Aoki S, Suzuki H (2013) RANKL subcellular trafficking and regulatory mechanisms in osteocytes. J Bone Miner Res doi. doi: 10.1002/jbmr.1941 Google Scholar
  36. 36.
    Bellido T, Saini V, Pajevic PD (2013) Effects of PTH on osteocyte function. Bone 54:250–257PubMedCrossRefGoogle Scholar
  37. 37.
    Rhee Y, Allen MR, Condon K, Plotkin LI, Lezcano V, Vyas K, O’Brien CA et al (2009) PTH receptor signaling in osteocytes governs periosteal bone formation and intra-cortical remodeling: divergent role of Sost and the Wnt pathway. J Bone Miner Res 24:S78CrossRefGoogle Scholar
  38. 38.
    O’Brien CA, Plotkin LI, Galli C, Goellner J, Gortazar AR, Allen MR, Robling AG et al (2008) Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS One 3:e2942PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Qing H, Ardeshirpour L, Pajevic PD, Dusevich V, Jahn K, Kato S, Wysolmerski J et al (2012) Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J Bone Miner Res 27:1018–1029PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Harris SE, MacDougall M, Horn D, Woodruff K, Zimmer SN, Rebel VI, Fajardo R et al (2012) Meox2Cre-mediated disruption of CSF-1 leads to osteopetrosis and osteocyte defects. Bone 50:42–53PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Noble BS, Peet N, Stevens HY, Brabbs A, Mosley JR, Reilly GC, Reeve J et al (2003) Mechanical loading: biphasic osteocyte survival and the targeting of osteoclasts for bone destruction in rat cortical bone. Am J Physiol Cell Physiol 284:C934–C943PubMedCrossRefGoogle Scholar
  42. 42.
    Bellido T, Plotkin LI (2011) Novel actions of bisphosphonates in bone: preservation of osteoblast and osteocyte viability. Bone 49:50–55PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Jilka RL, Bellido T, Almeida M, Plotkin LI, O’Brien CA, Weinstein RS, Manolagas SC (2008) Apoptosis in bone cells. In: Bilezikian JP, Raisz LG, Martin TJ (eds) Principles of bone biology. Academic Press, San Diego, pp 237–261CrossRefGoogle Scholar
  44. 44.
    Tomkinson A, Reeve J, Shaw RW, Noble BS (1997) The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J Clin Endocrinol Metab 82:3128–3135PubMedGoogle Scholar
  45. 45.
    Tomkinson A, Gevers EF, Wit JM, Reeve J, Noble BS (1998) The role of estrogen in the control of rat osteocyte apoptosis. J Bone Miner Res 13:1243–1250PubMedCrossRefGoogle Scholar
  46. 46.
    Huber C, Collishaw S, Mosley JR, Reeve J, Noble BS (2007) Selective estrogen receptor modulator inhibits osteocyte apoptosis during abrupt estrogen withdrawal: implications for bone quality maintenance. Calcif Tissue Int 81:139–144PubMedCrossRefGoogle Scholar
  47. 47.
    Mann V, Huber C, Kogianni G, Collins F, Noble B (2007) The antioxidant effect of estrogen and selective estrogen receptor modulators in the inhibition of osteocyte apoptosis in vitro. Bone 40:674–684PubMedCrossRefGoogle Scholar
  48. 48.
    Kousteni S, Bellido T, Plotkin LI, O’Brien CA, Bodenner DL, Han L, Han K et al (2001) Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104:719–730PubMedGoogle Scholar
  49. 49.
    Kousteni S, Chen JR, Bellido T, Han L, Ali AA, O’Brien CA, Plotkin LI et al (2002) Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science 298:843–846PubMedCrossRefGoogle Scholar
  50. 50.
    Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids: potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Almeida M, Han L, Martin-Millan M, Plotkin LI, Stewart SA, Roberson PK, Kousteni S et al (2007) Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem 282:27285–27297PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Bellido T (2010) Antagonistic interplay between mechanical forces and glucocorticoids in bone: a tale of kinases. J Cell Biochem 111:1–6PubMedCrossRefGoogle Scholar
  53. 53.
    Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T (1999) Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 104:1363–1374PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Plotkin LI, Mathov I, Aguirre JI, Parfitt AM, Manolagas SC, Bellido T (2005) Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases and ERKs. Am J Physiol Cell Physiol 289:C633–C643PubMedCrossRefGoogle Scholar
  55. 55.
    Bakker A, Klein-Nulend J, Burger E (2004) Shear stress inhibits while disuse promotes osteocyte apoptosis. Biochem Biophys Res Commun 320:1163–1168PubMedCrossRefGoogle Scholar
  56. 56.
    Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt signaling. Bone 42:606–615PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Armstrong VJ, Muzylak M, Sunters A, Zaman G, Saxon LK, Price JS, Lanyon LE (2007) Wnt/β-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor α. J Biol Chem 282:20715–20727PubMedCrossRefGoogle Scholar
  58. 58.
    Sunters A, Armstrong VJ, Zaman G, Kypta RM, Kawano Y, Lanyon LE, Price JS (2010) Mechano-transduction in osteoblastic cells involves strain-regulated, estrogen receptor α-mediated, control of IGF-IR sensitivity to ambient IGF, leading to PI3-K/ AKT dependent, Wnt/LRP5 receptor-independent activation of β-catenin signaling. J Biol Chem 285:8743–8758PubMedCrossRefGoogle Scholar
  59. 59.
    Almeida M, Han L, Bellido T, Manolagas SC, Kousteni S (2005) Wnt proteins prevent apoptosis of both uncommitted osteoblast progenitors and differentiated osteoblasts by beta-catenin-dependent and -independent signaling cascades involving Src/ERK and phosphatidylinositol 3-kinase/AKT. J Biol Chem 280:41342–41351PubMedCrossRefGoogle Scholar
  60. 60.
    Gortazar AR, Martin-Millan M, Bravo B, Plotkin LI, Bellido T (2013) Crosstalk between caveolin-1/extracellular signal–regulated kinase (ERK) and ß-catenin survival pathways in osteocyte mechanotransduction. J Biol Chem 288:8168–8175PubMedCrossRefGoogle Scholar
  61. 61.
    Verborgt O, Gibson G, Schaffler MB (2000) Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res 15:60–67PubMedCrossRefGoogle Scholar
  62. 62.
    Verborgt O, Tatton NA, Majeska RJ, Schaffler MB (2002) Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation? J Bone Miner Res 17:907–914PubMedCrossRefGoogle Scholar
  63. 63.
    Bellido T (2007) Osteocyte apoptosis induces bone resorption and impairs the skeletal response to weightlessness. Bonekey Osteovision 4:252–256CrossRefGoogle Scholar
  64. 64.
    Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M et al (2007) Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab 5:464–475PubMedCrossRefGoogle Scholar
  65. 65.
    Yang J, Shah R, Robling AG, Templeton E, Yang H, Tracey KJ, Bidwell JP (2008) HMGB1 is a bone-active cytokine. J Cell Physiol 214:730–739PubMedCrossRefGoogle Scholar
  66. 66.
    Jilka RL, Noble B, Weinstein RS (2013) Osteocyte apoptosis. Bone 54:264–271PubMedCrossRefGoogle Scholar
  67. 67.
    Kogianni G, Mann V, Noble BS (2008) Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localised bone destruction. J Bone Miner Res 23:915–927PubMedCrossRefGoogle Scholar
  68. 68.
    Kennedy OD, Herman BC, Laudier DM, Majeska RJ, Sun HB, Schaffler MB (2012) Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations. Bone 50:1115–1122PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Marcus R (2002) Mechanisms of exercise effects on bone. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology. Academic Press, San Diego, pp 1477–1488CrossRefGoogle Scholar
  70. 70.
    Bikle DD, Halloran BP, Morey-Holton E (1997) Spaceflight and the skeleton: lessons for the earthbound. Gravit Space Biol Bull 10:119–135PubMedGoogle Scholar
  71. 71.
    Kousteni S, Han L, Chen JR, Almeida M, Plotkin LI, Bellido T, Manolagas SC (2003) Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids. J Clin Invest 111:1651–1664PubMedCentralPubMedGoogle Scholar
  72. 72.
    Plotkin LI, Manolagas SC, Bellido T (2002) Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem 277:8648–8657PubMedCrossRefGoogle Scholar
  73. 73.
    Plotkin LI, Bellido T (2001) Bisphosphonate-induced, hemichannel-mediated, anti-apoptosis through the Src/ERK pathway: a gap junction–independent action of connexin43. Cell Adhes Commun 8:377–382CrossRefGoogle Scholar
  74. 74.
    Parfitt AM (2002) Life history of osteocytes: relationship to bone age, bone remodeling, and bone fragility. J Musculoskelet Neuronal Interact 2:499–500PubMedGoogle Scholar
  75. 75.
    Parfitt AM (2002) Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone 30:5–7PubMedCrossRefGoogle Scholar
  76. 76.
    Manolagas SC, Parfitt AM (2010) What old means to bone. Trends Endocrinol Metab 21:369–374PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Manolagas SC (2010) From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 31:266–300PubMedCrossRefGoogle Scholar
  78. 78.
    Weinstein RS, Wan C, Liu Q, Wang Y, Almeida M, O’Brien CA, Thostenson J et al (2009) Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in 21-month-old mice. Aging Cell 9:147–161PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Bivi N, Condon KW, Allen MR, Farlow N, Passeri G, Brun L, Rhee Y et al (2012) Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation. J Bone Miner Res 27:374–389PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Plotkin LI, Bellido T (2013) Beyond gap junctions: connexin43 and bone cell signaling. Bone 52:157–166PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Zhang Y, Paul EM, Sathyendra V, Davidson A, Bronson S, Srinivasan S, Gross TS et al (2011) Enhanced osteoclastic resorption and responsiveness to mechanical load in gap junction deficient bone. PLoS One 6:e23516PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Grimston SK, Brodt MD, Silva MJ, Civitelli R (2008) Attenuated response to in vivo mechanical loading in mice with conditional osteoblast ablation of the connexin43 gene (Gja1). J Bone Miner Res 23:879–886PubMedCrossRefGoogle Scholar
  83. 83.
    Qiu S, Rao DS, Palnitkar S, Parfitt AM (2002) Age and distance from the surface but not menopause reduce osteocyte density in human cancellous bone. Bone 31:313–318PubMedCrossRefGoogle Scholar
  84. 84.
    Robinson JA, Chatterjee-Kishore M, Yaworsky PJ, Cullen DM, Zhao W, Li C, Kharode Y et al (2006) WNT/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem 281:31720–31728PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisUSA
  2. 2.Division of Endocrinology, Department of MedicineIndiana University School of MedicineIndianapolisUSA
  3. 3.Roudebush Veterans Administration Medical CenterIndianapolisUSA

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