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Published in: Current Osteoporosis Reports 1/2014

01-03-2014 | Skeletal Biology and Regulation (MR Forwood and A Robling, Section Editors)

Apoptotic Osteocytes and the Control of Targeted Bone Resorption

Author: Lilian I. Plotkin

Published in: Current Osteoporosis Reports | Issue 1/2014

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Abstract

Studies from the 1950s and 1960s already recognize the fact that osteocytes, although long living cells, die, as evidenced by accumulation of osteocytic lacunae devoid of cells. More recently, it was demonstrated that these cells die by apoptosis. The rate of osteocyte apoptosis is regulated by the age of the bone, as well as by systemic hormones, local growth factors, cytokines, pharmacological agents, and mechanical forces. Apoptotic osteocytes, in turn, recruit osteoclasts to initiate targeted bone resorption. This results in the removal of “dead” bone and may improve the mechanical properties of the skeleton. However, the molecular regulators of osteocyte survival and targeted bone remodeling are not completely known. In this review, the current knowledge on the molecular mechanism that lead to osteocyte death or survival, and the signals that mediate targeted bone resorption is discussed.
Literature
1.
go back to reference Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int. 2013;94:25–34. Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int. 2013;94:25–34.
2.
go back to reference Noble BS, Reeve J. Osteocyte function, osteocyte death and bone fracture resistance. Mol Cell Endocrinol. 2000;159:7–13.PubMedCrossRef Noble BS, Reeve J. Osteocyte function, osteocyte death and bone fracture resistance. Mol Cell Endocrinol. 2000;159:7–13.PubMedCrossRef
3.
go back to reference Frost HM. In vivo osteocyte death. J Bone Joint Surg Am. 1960;42-A:138–43.PubMed Frost HM. In vivo osteocyte death. J Bone Joint Surg Am. 1960;42-A:138–43.PubMed
4.
go back to reference Almeida M, Han L, Martin-Millan M, et al. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem. 2007;282:27285–97.PubMedCentralPubMedCrossRef Almeida M, Han L, Martin-Millan M, et al. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem. 2007;282:27285–97.PubMedCentralPubMedCrossRef
5.
go back to reference Tomkinson A, Reeve J, Shaw RW, et al. The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J Clin Endocrinol Metab. 1997;82:3128–35.PubMed Tomkinson A, Reeve J, Shaw RW, et al. The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J Clin Endocrinol Metab. 1997;82:3128–35.PubMed
6.
go back to reference Kousteni S, Bellido T, Plotkin LI, et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell. 2001;104:719–30.PubMed Kousteni S, Bellido T, Plotkin LI, et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell. 2001;104:719–30.PubMed
7.
go back to reference Weinstein RS, Jilka RL, Parfitt AM, et al. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids: potential mechanisms of their deleterious effects on bone. J Clin Invest. 1998;102:274–82.PubMedCentralPubMedCrossRef Weinstein RS, Jilka RL, Parfitt AM, et al. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids: potential mechanisms of their deleterious effects on bone. J Clin Invest. 1998;102:274–82.PubMedCentralPubMedCrossRef
8.
go back to reference Aguirre JI, Plotkin LI, Stewart SA, et al. Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res. 2006;21:605–15.PubMedCrossRef Aguirre JI, Plotkin LI, Stewart SA, et al. Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res. 2006;21:605–15.PubMedCrossRef
9.
go back to reference Morse LR, Xu Y, Solomon B, et al. Severe spinal cord injury causes immediate multi-cellular dysfunction at the chondro-osseous junction. Transl Stroke Res. 2011;2:643–50.PubMedCentralPubMedCrossRef Morse LR, Xu Y, Solomon B, et al. Severe spinal cord injury causes immediate multi-cellular dysfunction at the chondro-osseous junction. Transl Stroke Res. 2011;2:643–50.PubMedCentralPubMedCrossRef
10.
go back to reference Verborgt O, Gibson G, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res. 2000;15:60–7.PubMedCrossRef Verborgt O, Gibson G, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res. 2000;15:60–7.PubMedCrossRef
11.
go back to reference Jilka RL, Weinstein RS, Bellido T, et al. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest. 1999;104:439–46.PubMedCentralPubMedCrossRef Jilka RL, Weinstein RS, Bellido T, et al. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest. 1999;104:439–46.PubMedCentralPubMedCrossRef
12.
go back to reference Plotkin LI, Weinstein RS, Parfitt AM, et al. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest. 1999;104:1363–74.PubMedCentralPubMedCrossRef Plotkin LI, Weinstein RS, Parfitt AM, et al. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest. 1999;104:1363–74.PubMedCentralPubMedCrossRef
13.
go back to reference Gohel A, McCarthy MB, Gronowicz G. Estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro. Endocrinology. 1999;140:5339–47.PubMed Gohel A, McCarthy MB, Gronowicz G. Estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro. Endocrinology. 1999;140:5339–47.PubMed
15.
go back to reference Jilka RL, Bellido T, Almeida M, Plotkin LI, O'Brien CA, Weinstein RS, et al. Apoptosis in bone cells. In: Bilezikian JP, Raisz LG, Martin TJ, editors. Principles of bone biology. San Diego, San Francisco, New York, London, Sydney, Tokyo: Academic Press; 2008. p. 237–61.CrossRef Jilka RL, Bellido T, Almeida M, Plotkin LI, O'Brien CA, Weinstein RS, et al. Apoptosis in bone cells. In: Bilezikian JP, Raisz LG, Martin TJ, editors. Principles of bone biology. San Diego, San Francisco, New York, London, Sydney, Tokyo: Academic Press; 2008. p. 237–61.CrossRef
16.••
go back to reference Jilka RL, O'Brien CA, Roberson PK, et al. Dysapoptosis of osteoblasts and osteocytes increases cancellous bone formation but exaggerates bone porosity with age. J Bone Miner Res. 2014;29:103–17. Reports the effect of preventing osteocyte apoptosis on gene expression and bone remodeling. Jilka RL, O'Brien CA, Roberson PK, et al. Dysapoptosis of osteoblasts and osteocytes increases cancellous bone formation but exaggerates bone porosity with age. J Bone Miner Res. 2014;29:103–17. Reports the effect of preventing osteocyte apoptosis on gene expression and bone remodeling.
17.
go back to reference Weinstein RS, Nicholas RW, Manolagas SC. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab. 2000;85:2907–12.PubMed Weinstein RS, Nicholas RW, Manolagas SC. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab. 2000;85:2907–12.PubMed
18.
go back to reference Plotkin LI, Manolagas SC, Bellido T. Glucocorticoids induce osteocyte apoptosis by blocking focal adhesion kinase-mediated survival: evidence for inside-out signaling leading to anoikis. J Biol Chem. 2007;282:24120–30.PubMedCrossRef Plotkin LI, Manolagas SC, Bellido T. Glucocorticoids induce osteocyte apoptosis by blocking focal adhesion kinase-mediated survival: evidence for inside-out signaling leading to anoikis. J Biol Chem. 2007;282:24120–30.PubMedCrossRef
19.
go back to reference Canalis E, Delany AM. Mechanisms of glucocorticoid action in bone. Ann N Y Acad Sci. 2002;966:73–81.PubMedCrossRef Canalis E, Delany AM. Mechanisms of glucocorticoid action in bone. Ann N Y Acad Sci. 2002;966:73–81.PubMedCrossRef
20.
go back to reference Wang FS, Lin CL, Chen YJ, et al. Secreted frizzled-related protein 1 (SFRP1) modulates glucocorticoid attenuation of osteogenic activities and bone mass. Endocrinology. 2005;146:2415–23.PubMedCrossRef Wang FS, Lin CL, Chen YJ, et al. Secreted frizzled-related protein 1 (SFRP1) modulates glucocorticoid attenuation of osteogenic activities and bone mass. Endocrinology. 2005;146:2415–23.PubMedCrossRef
21.
go back to reference Almeida M, Han L, Ambrogini E, et al. Glucocorticoids and tumor necrosis factor (TNF) alpha increase oxidative stress and suppress WNT signaling in osteoblasts. J Biol Chem. 2011;286:44326–35.PubMedCrossRef Almeida M, Han L, Ambrogini E, et al. Glucocorticoids and tumor necrosis factor (TNF) alpha increase oxidative stress and suppress WNT signaling in osteoblasts. J Biol Chem. 2011;286:44326–35.PubMedCrossRef
22.
go back to reference Jia J, Yao W, Guan M, et al. Glucocorticoid dose determines osteocyte cell fate. FASEB J. 2011;25:3366–76.PubMedCrossRef Jia J, Yao W, Guan M, et al. Glucocorticoid dose determines osteocyte cell fate. FASEB J. 2011;25:3366–76.PubMedCrossRef
23.
go back to reference Weinstein RS, Wan C, Liu Q, et al. Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in 21-month-old mice. Aging Cell. 2009;9:147–61.PubMedCentralPubMedCrossRef Weinstein RS, Wan C, Liu Q, et al. Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in 21-month-old mice. Aging Cell. 2009;9:147–61.PubMedCentralPubMedCrossRef
24.
go back to reference Noble BS, Peet N, Stevens HY, et al. Mechanical loading: biphasic osteocyte survival and the targeting of osteoclasts for bone destruction in rat cortical bone. Am J Physiol Cell Physiol. 2003;284:C934–43.PubMedCrossRef Noble BS, Peet N, Stevens HY, et al. Mechanical loading: biphasic osteocyte survival and the targeting of osteoclasts for bone destruction in rat cortical bone. Am J Physiol Cell Physiol. 2003;284:C934–43.PubMedCrossRef
25.
go back to reference Lin C, Jiang X, Dai Z, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res. 2009;24:1651–61.PubMedCrossRef Lin C, Jiang X, Dai Z, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res. 2009;24:1651–61.PubMedCrossRef
26.
go back to reference Verborgt O, Tatton NA, Majeska RJ, et al. Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation? J Bone Miner Res. 2002;17:907–14.PubMedCrossRef Verborgt O, Tatton NA, Majeska RJ, et al. Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation? J Bone Miner Res. 2002;17:907–14.PubMedCrossRef
27.
go back to reference Bellido T, Ali AA, Plotkin LI, et al. Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem. 2003;278:50259–72.PubMedCrossRef Bellido T, Ali AA, Plotkin LI, et al. Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem. 2003;278:50259–72.PubMedCrossRef
28.
go back to reference Bivi N, Lezcano V, Romanello M, et al. Connexin43 interacts with barrestin: a prerequisite for osteoblast survival induced by parathyroid hormone. J Cell Biochem. 2011;112:2920–30.PubMedCentralPubMedCrossRef Bivi N, Lezcano V, Romanello M, et al. Connexin43 interacts with barrestin: a prerequisite for osteoblast survival induced by parathyroid hormone. J Cell Biochem. 2011;112:2920–30.PubMedCentralPubMedCrossRef
29.
go back to reference Rogers MJ, Crockett JC, Coxon FP, et al. Biochemical and molecular mechanisms of action of bisphosphonates. Bone. 2011;49:34–41.PubMedCrossRef Rogers MJ, Crockett JC, Coxon FP, et al. Biochemical and molecular mechanisms of action of bisphosphonates. Bone. 2011;49:34–41.PubMedCrossRef
30.
go back to reference Plotkin LI, Manolagas SC, Bellido T. Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem. 2002;277:8648–57.PubMedCrossRef Plotkin LI, Manolagas SC, Bellido T. Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem. 2002;277:8648–57.PubMedCrossRef
31.
go back to reference Plotkin LI, Lezcano V, Thostenson J, et al. Connexin 43 is required for the anti-apoptotic effect of bisphosphonates on osteocytes and osteoblasts in vivo. J Bone Miner Res. 2008;23:1712–21.PubMedCrossRef Plotkin LI, Lezcano V, Thostenson J, et al. Connexin 43 is required for the anti-apoptotic effect of bisphosphonates on osteocytes and osteoblasts in vivo. J Bone Miner Res. 2008;23:1712–21.PubMedCrossRef
32.
go back to reference Plotkin LI, Bivi N, Bellido T. A bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice. Bone. 2011;49:122–7.PubMedCentralPubMedCrossRef Plotkin LI, Bivi N, Bellido T. A bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice. Bone. 2011;49:122–7.PubMedCentralPubMedCrossRef
33.
go back to reference Plotkin LI, Aguirre JI, Kousteni S, et al. Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of ERK activation. J Biol Chem. 2005;280:7317–25.PubMedCrossRef Plotkin LI, Aguirre JI, Kousteni S, et al. Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of ERK activation. J Biol Chem. 2005;280:7317–25.PubMedCrossRef
34.
go back to reference Plotkin LI, Manolagas SC, Bellido T. Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their anti-apoptotic effects on osteoblasts/osteocytes with novel analogs. Bone. 2006;39:443–52.PubMedCrossRef Plotkin LI, Manolagas SC, Bellido T. Dissociation of the pro-apoptotic effects of bisphosphonates on osteoclasts from their anti-apoptotic effects on osteoblasts/osteocytes with novel analogs. Bone. 2006;39:443–52.PubMedCrossRef
35.
go back to reference Tomkinson A, Gevers EF, Wit JM, et al. The role of estrogen in the control of rat osteocyte apoptosis. J Bone Miner Res. 1998;13:1243–50.PubMedCrossRef Tomkinson A, Gevers EF, Wit JM, et al. The role of estrogen in the control of rat osteocyte apoptosis. J Bone Miner Res. 1998;13:1243–50.PubMedCrossRef
36.
go back to reference Kousteni S, Chen JR, Bellido T, et al. Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science. 2002;298:843–6.PubMedCrossRef Kousteni S, Chen JR, Bellido T, et al. Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science. 2002;298:843–6.PubMedCrossRef
37.
go back to reference Huber C, Collishaw S, Mosley JR, et al. Selective estrogen receptor modulator inhibits osteocyte apoptosis during abrupt estrogen withdrawal: implications for bone quality maintenance. Calcif Tissue Int. 2007;81:139–44.PubMedCrossRef Huber C, Collishaw S, Mosley JR, et al. Selective estrogen receptor modulator inhibits osteocyte apoptosis during abrupt estrogen withdrawal: implications for bone quality maintenance. Calcif Tissue Int. 2007;81:139–44.PubMedCrossRef
38.
go back to reference Kousteni S, Han L, Chen JR, et al. Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids. J Clin Invest. 2003;111:1651–64.PubMedCentralPubMedCrossRef Kousteni S, Han L, Chen JR, et al. Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids. J Clin Invest. 2003;111:1651–64.PubMedCentralPubMedCrossRef
39.
go back to reference van Essen HW, Holzmann PJ, Blankenstein MA, et al. Effect of raloxifene treatment on osteocyte apoptosis in postmenopausal women. Calcif Tissue Int. 2007;81:183–90.PubMedCentralPubMedCrossRef van Essen HW, Holzmann PJ, Blankenstein MA, et al. Effect of raloxifene treatment on osteocyte apoptosis in postmenopausal women. Calcif Tissue Int. 2007;81:183–90.PubMedCentralPubMedCrossRef
40.
go back to reference Plotkin LI, Mathov I, Aguirre JI, et al. Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs. Am J Physiol Cell Physiol. 2005;289:C633–43.PubMedCrossRef Plotkin LI, Mathov I, Aguirre JI, et al. Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs. Am J Physiol Cell Physiol. 2005;289:C633–43.PubMedCrossRef
41.
go back to reference Aguirre JI, Plotkin LI, Gortazar AR, et al. A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J Biol Chem. 2007;282:25501–8.PubMedCrossRef Aguirre JI, Plotkin LI, Gortazar AR, et al. A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J Biol Chem. 2007;282:25501–8.PubMedCrossRef
42.
go back to reference Kitase Y, Barragan L, Jiang JX, et al. Mechanical induction of PGE(2) in osteocytes blocks glucocorticoid induced apoptosis through both the beta-catenin and PKA pathways. J Bone Miner Res. 2010;25:2657–68.PubMedCrossRef Kitase Y, Barragan L, Jiang JX, et al. Mechanical induction of PGE(2) in osteocytes blocks glucocorticoid induced apoptosis through both the beta-catenin and PKA pathways. J Bone Miner Res. 2010;25:2657–68.PubMedCrossRef
43.
go back to reference Frost HM. Bone's mechanostat: a 2003 update. Anat Rec. 2003;275A:1081–101.CrossRef Frost HM. Bone's mechanostat: a 2003 update. Anat Rec. 2003;275A:1081–101.CrossRef
44.
go back to reference Noble BS, Stevens H, Loveridge N, et al. Identification of apoptotic changes in osteocytes in normal and pathological human bone. Bone. 1997;20:273–82.PubMedCrossRef Noble BS, Stevens H, Loveridge N, et al. Identification of apoptotic changes in osteocytes in normal and pathological human bone. Bone. 1997;20:273–82.PubMedCrossRef
45.
go back to reference Elmardi AS, Katchburian MV, Katchburian E. Electron microscopy of developing calvaria reveals images that suggest that osteoclasts engulf and destroy osteocytes during bone resorption. Calcif Tissue Int. 1990;46:239–45.PubMedCrossRef Elmardi AS, Katchburian MV, Katchburian E. Electron microscopy of developing calvaria reveals images that suggest that osteoclasts engulf and destroy osteocytes during bone resorption. Calcif Tissue Int. 1990;46:239–45.PubMedCrossRef
46.
go back to reference Boabaid F, Cerri PS, Katchburian E. Apoptotic bone cells may be engulfed by osteoclasts during alveolar bone resorption in young rats. Tissue Cell. 2001;33:318–25.PubMedCrossRef Boabaid F, Cerri PS, Katchburian E. Apoptotic bone cells may be engulfed by osteoclasts during alveolar bone resorption in young rats. Tissue Cell. 2001;33:318–25.PubMedCrossRef
47.
go back to reference Cerri PS, Boabaid F, Katchburian E. Combined TUNEL and TRAP methods suggest that apoptotic bone cells are inside vacuoles of alveolar bone osteoclasts in young rats. J Periodontal Res. 2003;38:223–6.PubMedCrossRef Cerri PS, Boabaid F, Katchburian E. Combined TUNEL and TRAP methods suggest that apoptotic bone cells are inside vacuoles of alveolar bone osteoclasts in young rats. J Periodontal Res. 2003;38:223–6.PubMedCrossRef
48.
go back to reference Cardoso L, Herman BC, Verborgt O, et al. Osteocyte apoptosis controls activation of intracortical resorption in response to bone fatigue. J Bone Miner Res. 2009;24:597–605.PubMedCrossRef Cardoso L, Herman BC, Verborgt O, et al. Osteocyte apoptosis controls activation of intracortical resorption in response to bone fatigue. J Bone Miner Res. 2009;24:597–605.PubMedCrossRef
50.
go back to reference Tatsumi S, Ishii K, Amizuka N, et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007;5:464–75.PubMedCrossRef Tatsumi S, Ishii K, Amizuka N, et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007;5:464–75.PubMedCrossRef
51.
go back to reference Bivi N, Condon KW, Allen MR, et al. Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation. J Bone Miner Res. 2012;27:374–89.PubMedCentralPubMedCrossRef Bivi N, Condon KW, Allen MR, et al. Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation. J Bone Miner Res. 2012;27:374–89.PubMedCentralPubMedCrossRef
52.
go back to reference Lloyd SA, Loiselle AE, Zhang Y, et al. Connexin 43 deficiency desensitizes bone to the effects of mechanical unloading through modulation of both arms of bone remodeling. Bone. 2013;57:76–83.PubMedCrossRef Lloyd SA, Loiselle AE, Zhang Y, et al. Connexin 43 deficiency desensitizes bone to the effects of mechanical unloading through modulation of both arms of bone remodeling. Bone. 2013;57:76–83.PubMedCrossRef
53.
go back to reference Schaffler MB, Cheung WY, Majeska R, et al. Osteocytes: master orchestrators of bone. Calcif Tissue Int. 2013;94:5–24. Schaffler MB, Cheung WY, Majeska R, et al. Osteocytes: master orchestrators of bone. Calcif Tissue Int. 2013;94:5–24.
54.•
go back to reference Kennedy OD, Herman BC, Laudier DM, et al. Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations. Bone. 2012;50:1115–22. Reports the temporal relationships between injury, osteocyte apoptosis, and pro-osteoclastogenic signaling following excess loading. Kennedy OD, Herman BC, Laudier DM, et al. Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations. Bone. 2012;50:1115–22. Reports the temporal relationships between injury, osteocyte apoptosis, and pro-osteoclastogenic signaling following excess loading.
55.
go back to reference Wu AC, Morrison NA, Kelly WL, et al. MCP-1 expression is specifically regulated during activation of skeletal repair and remodeling. Calcif Tissue Int. 2013;92:566–75.PubMedCrossRef Wu AC, Morrison NA, Kelly WL, et al. MCP-1 expression is specifically regulated during activation of skeletal repair and remodeling. Calcif Tissue Int. 2013;92:566–75.PubMedCrossRef
56.
go back to reference Zhang Y, Paul EM, Sathyendra V, et al. Enhanced osteoclastic resorption and responsiveness to mechanical load in gap junction deficient bone. PLoS One. 2011;6:e23516.PubMedCentralPubMedCrossRef Zhang Y, Paul EM, Sathyendra V, et al. Enhanced osteoclastic resorption and responsiveness to mechanical load in gap junction deficient bone. PLoS One. 2011;6:e23516.PubMedCentralPubMedCrossRef
57.
go back to reference Kogianni G, Mann V, Noble BS. Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction. J Bone Miner Res. 2008;23:915–27.PubMedCrossRef Kogianni G, Mann V, Noble BS. Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction. J Bone Miner Res. 2008;23:915–27.PubMedCrossRef
58.
go back to reference Yang J, Shah R, Robling AG, et al. HMGB1 is a bone-active cytokine. J Cell Physiol. 2008;214:730–9.PubMedCrossRef Yang J, Shah R, Robling AG, et al. HMGB1 is a bone-active cytokine. J Cell Physiol. 2008;214:730–9.PubMedCrossRef
60.
go back to reference Zhou Z, Han JY, Xi CX, et al. HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE. J Bone Miner Res. 2008;23:1084–96.PubMedCrossRef Zhou Z, Han JY, Xi CX, et al. HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE. J Bone Miner Res. 2008;23:1084–96.PubMedCrossRef
61.
go back to reference Taniguchi N, Yoshida K, Ito T, et al. Stage-specific secretion of HMGB1 in cartilage regulates endochondral ossification. Mol Cell Biol. 2007;27:5650–63.PubMedCentralPubMedCrossRef Taniguchi N, Yoshida K, Ito T, et al. Stage-specific secretion of HMGB1 in cartilage regulates endochondral ossification. Mol Cell Biol. 2007;27:5650–63.PubMedCentralPubMedCrossRef
Metadata
Title
Apoptotic Osteocytes and the Control of Targeted Bone Resorption
Author
Lilian I. Plotkin
Publication date
01-03-2014
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 1/2014
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-014-0194-3

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