Skip to main content
Erschienen in: Wiener Medizinische Wochenschrift 3-4/2015

01.02.2015 | main topic

Molecular and cellular basis of bone resorption

verfasst von: Reinhard Gruber, PhD

Erschienen in: Wiener Medizinische Wochenschrift | Ausgabe 3-4/2015

Einloggen, um Zugang zu erhalten

Summary

Osteoclast research has an exciting history and a challenging future. More than 3 decades ago, it became evident that bone-resorbing osteoclasts are of hematopoietic origin and are ultimately linked to the “basic multicellular unit,” where they team up with the other cell types, including bone-forming osteoblasts. Since 2 decades, we have learned about the signaling pathways controlling genes relevant for osteoclastogenesis and bone resorption. It took another decade until the hypothesized “osteoclast differentiation” factor was discovered and was translated into an approved pharmacologic strategy. Here, the focus is on another molecular target, cathepsin K, a cysteine protease being released by the osteoclast into the resorption compartment. Genetic deletion and pharmacological blocking of cathepsin K reduces bone resorption but with ongoing bone formation. This observation not only holds great promise to become a new pharmacologic strategy, but it also provides new insights into the coordinated work of cells in the “basic multicellular unit” and thus, bridges the history and future of osteoclast research. This article is a short primer on osteoclast biology for readers of the special issue on odanacatib, a cathepsin K inhibitor.
Literatur
1.
Zurück zum Zitat Frost HM. A 2003 update of bone physiology and Wolff‘s Law for clinicians. Angle Orthod. 2004;74:3–15.PubMed Frost HM. A 2003 update of bone physiology and Wolff‘s Law for clinicians. Angle Orthod. 2004;74:3–15.PubMed
2.
Zurück zum Zitat Parfitt AM. Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem. 1994;55:273–86.CrossRefPubMed Parfitt AM. Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem. 1994;55:273–86.CrossRefPubMed
3.
Zurück zum Zitat Sims NA, Martin TJ. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep. 2014;3:481.PubMedCentralPubMed Sims NA, Martin TJ. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep. 2014;3:481.PubMedCentralPubMed
4.
Zurück zum Zitat Delaisse JM. The reversal phase of the bone-remodeling cycle: cellular prerequisites for coupling resorption and formation. Bonekey Rep. 2014;3:561. Delaisse JM. The reversal phase of the bone-remodeling cycle: cellular prerequisites for coupling resorption and formation. Bonekey Rep. 2014;3:561.
5.
Zurück zum Zitat Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21:115–37.PubMed Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21:115–37.PubMed
8.
Zurück zum Zitat Cappariello A, Maurizi A, Veeriah V, Teti A. The Great Beauty of the osteoclast. Arch Biochem Biophys. 2014;558C:70–8.CrossRef Cappariello A, Maurizi A, Veeriah V, Teti A. The Great Beauty of the osteoclast. Arch Biochem Biophys. 2014;558C:70–8.CrossRef
9.
Zurück zum Zitat Novinec M, Lenarcic B. Cathepsin K: a unique collagenolytic cysteine peptidase. Biol Chem. 2013;394:1163–79.CrossRefPubMed Novinec M, Lenarcic B. Cathepsin K: a unique collagenolytic cysteine peptidase. Biol Chem. 2013;394:1163–79.CrossRefPubMed
10.
Zurück zum Zitat Hlaing TT, Compston JE. Biochemical markers of bone turnover—uses and limitations. Ann Clin Biochem. 2014;51:189–202.CrossRefPubMed Hlaing TT, Compston JE. Biochemical markers of bone turnover—uses and limitations. Ann Clin Biochem. 2014;51:189–202.CrossRefPubMed
11.
Zurück zum Zitat Chambers TJ. Regulation of osteoclast development and function. In: Rifkin BR, Gay CV, editors. Biology and physiology of the osteoclast. Boca Raton: CRC Press; 1992. S. 105–28. Chambers TJ. Regulation of osteoclast development and function. In: Rifkin BR, Gay CV, editors. Biology and physiology of the osteoclast. Boca Raton: CRC Press; 1992. S. 105–28.
12.
Zurück zum Zitat Marks SC, Jr. The origin of osteoclasts: evidence, clinical implications and investigative challenges of an extra-skeletal source. J Oral Pathol. 1983;12:226–56.CrossRefPubMed Marks SC, Jr. The origin of osteoclasts: evidence, clinical implications and investigative challenges of an extra-skeletal source. J Oral Pathol. 1983;12:226–56.CrossRefPubMed
13.
Zurück zum Zitat Takahashi N, Yamana H, Yoshiki S, Roodman GD, Mundy GR, Jones SJ, Boyde A, Suda T. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology. 1988;122:1373–82.CrossRefPubMed Takahashi N, Yamana H, Yoshiki S, Roodman GD, Mundy GR, Jones SJ, Boyde A, Suda T. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology. 1988;122:1373–82.CrossRefPubMed
14.
Zurück zum Zitat Suda T, Takahashi N, Martin TJ. Modulation of osteoclast differentiation. Endocr Rev. 1992;13:66–80.PubMed Suda T, Takahashi N, Martin TJ. Modulation of osteoclast differentiation. Endocr Rev. 1992;13:66–80.PubMed
15.
Zurück zum Zitat Jimi E, Nakamura I, Amano H, Taguchi Y, Tsurukai T, Tamura M, Takahashi N, Suda T. Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact. Endocrinology. 1996;137:2187–90. Jimi E, Nakamura I, Amano H, Taguchi Y, Tsurukai T, Tamura M, Takahashi N, Suda T. Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact. Endocrinology. 1996;137:2187–90.
16.
Zurück zum Zitat Tsuda E, Goto M, Mochizuki S, Yano K, Kobayashi F, Morinaga T, Higashio K. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Commun. 1997;234:137–42.CrossRefPubMed Tsuda E, Goto M, Mochizuki S, Yano K, Kobayashi F, Morinaga T, Higashio K. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Commun. 1997;234:137–42.CrossRefPubMed
17.
Zurück zum Zitat Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology. 1998;139:1329–37.PubMed Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology. 1998;139:1329–37.PubMed
18.
Zurück zum Zitat Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998;95:3597–602.CrossRefPubMedCentralPubMed Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A. 1998;95:3597–602.CrossRefPubMedCentralPubMed
19.
Zurück zum Zitat Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89:309–19.CrossRefPubMed Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89:309–19.CrossRefPubMed
20.
Zurück zum Zitat Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93:165–76.CrossRefPubMed Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93:165–76.CrossRefPubMed
21.
Zurück zum Zitat Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, Choi Y. TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J Exp Med. 1997;186:2075–80.CrossRefPubMedCentralPubMed Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, Choi Y. TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J Exp Med. 1997;186:2075–80.CrossRefPubMedCentralPubMed
22.
Zurück zum Zitat Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 1997;390:175–9.CrossRefPubMed Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 1997;390:175–9.CrossRefPubMed
23.
Zurück zum Zitat Nakashima T, Takayanagi H. Osteoimmunology: crosstalk between the immune and bone systems. J Clin Immunol. 2009;29:555–67.CrossRefPubMed Nakashima T, Takayanagi H. Osteoimmunology: crosstalk between the immune and bone systems. J Clin Immunol. 2009;29:555–67.CrossRefPubMed
24.
Zurück zum Zitat Theill LE, Boyle WJ, Penninger JM. RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol. 2002;20:795–823.CrossRefPubMed Theill LE, Boyle WJ, Penninger JM. RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol. 2002;20:795–823.CrossRefPubMed
25.
Zurück zum Zitat Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Leese PT, Dunstan CR. The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res. 2001;16:348–60.CrossRefPubMed Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Leese PT, Dunstan CR. The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res. 2001;16:348–60.CrossRefPubMed
26.
Zurück zum Zitat Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, Holmes GB, Dunstan CR, DePaoli AM. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19:1059–66.CrossRefPubMed Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, Holmes GB, Dunstan CR, DePaoli AM. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19:1059–66.CrossRefPubMed
27.
Zurück zum Zitat Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65.CrossRefPubMed Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65.CrossRefPubMed
28.
Zurück zum Zitat Sun L, Yu S. Efficacy and safety of denosumab versus zoledronic acid in patients with bone metastases: a systematic review and meta-analysis. Am J Clin Oncol. 2013;36:399–403.CrossRefPubMed Sun L, Yu S. Efficacy and safety of denosumab versus zoledronic acid in patients with bone metastases: a systematic review and meta-analysis. Am J Clin Oncol. 2013;36:399–403.CrossRefPubMed
29.
Zurück zum Zitat Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA, Wagner EF. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science. 1994;266:443–8.CrossRefPubMed Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA, Wagner EF. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science. 1994;266:443–8.CrossRefPubMed
30.
Zurück zum Zitat Iotsova V, Caamano J, Loy J, Yang Y, Lewin A, Bravo R. Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat Med. 1997;3:1285–9.CrossRefPubMed Iotsova V, Caamano J, Loy J, Yang Y, Lewin A, Bravo R. Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat Med. 1997;3:1285–9.CrossRefPubMed
31.
Zurück zum Zitat Ishida N, Hayashi K, Hoshijima M, Ogawa T, Koga S, Miyatake Y, Kumegawa M, Kimura T, Takeya T. Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator. J Biol Chem. 2002;277:41147–56.CrossRefPubMed Ishida N, Hayashi K, Hoshijima M, Ogawa T, Koga S, Miyatake Y, Kumegawa M, Kimura T, Takeya T. Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator. J Biol Chem. 2002;277:41147–56.CrossRefPubMed
32.
Zurück zum Zitat Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner EF, Mak TW, Kodama T, Taniguchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002;3:889–901.CrossRefPubMed Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner EF, Mak TW, Kodama T, Taniguchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002;3:889–901.CrossRefPubMed
33.
Zurück zum Zitat Koga T, Inui M, Inoue K, Kim S, Suematsu A, Kobayashi E, Iwata T, Ohnishi H, Matozaki T, Kodama T, Taniguchi T, Takayanagi H, Takai T. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature. 2004;428:758–63.CrossRefPubMed Koga T, Inui M, Inoue K, Kim S, Suematsu A, Kobayashi E, Iwata T, Ohnishi H, Matozaki T, Kodama T, Taniguchi T, Takayanagi H, Takai T. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature. 2004;428:758–63.CrossRefPubMed
34.
Zurück zum Zitat Barrow AD, Raynal N, Andersen TL, Slatter DA, Bihan D, Pugh N, Cella M, Kim T, Rho J, Negishi-Koga T, Delaisse JM, Takayanagi H, Lorenzo J, Colonna M, Farndale RW, Choi Y, Trowsdale J. OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. J Clin Invest. 2011;121:3505–16.CrossRefPubMedCentralPubMed Barrow AD, Raynal N, Andersen TL, Slatter DA, Bihan D, Pugh N, Cella M, Kim T, Rho J, Negishi-Koga T, Delaisse JM, Takayanagi H, Lorenzo J, Colonna M, Farndale RW, Choi Y, Trowsdale J. OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. J Clin Invest. 2011;121:3505–16.CrossRefPubMedCentralPubMed
35.
Zurück zum Zitat Kim K, Lee SH, Ha Kim J, Choi Y, Kim N. NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP). Mol Endocrinol. 2008;22:176–85.CrossRefPubMedCentralPubMed Kim K, Lee SH, Ha Kim J, Choi Y, Kim N. NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP). Mol Endocrinol. 2008;22:176–85.CrossRefPubMedCentralPubMed
36.
Zurück zum Zitat Yagi M, Ninomiya K, Fujita N, Suzuki T, Iwasaki R, Morita K, Hosogane N, Matsuo K, Toyama Y, Suda T, Miyamoto T. Induction of DC-STAMP by alternative activation and downstream signaling mechanisms. J Bone Miner Res. 2007;22:992–1001.CrossRefPubMed Yagi M, Ninomiya K, Fujita N, Suzuki T, Iwasaki R, Morita K, Hosogane N, Matsuo K, Toyama Y, Suda T, Miyamoto T. Induction of DC-STAMP by alternative activation and downstream signaling mechanisms. J Bone Miner Res. 2007;22:992–1001.CrossRefPubMed
37.
Zurück zum Zitat Lee SH, Rho J, Jeong D, Sul JY, Kim T, Kim N, Kang JS, Miyamoto T, Suda T, Lee SK, Pignolo RJ, Koczon-Jaremko B, Lorenzo J, Choi Y. v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation. Nat Med. 2006;12:1403–9.CrossRefPubMed Lee SH, Rho J, Jeong D, Sul JY, Kim T, Kim N, Kang JS, Miyamoto T, Suda T, Lee SK, Pignolo RJ, Koczon-Jaremko B, Lorenzo J, Choi Y. v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation. Nat Med. 2006;12:1403–9.CrossRefPubMed
38.
Zurück zum Zitat Miyamoto H, Suzuki T, Miyauchi Y, Iwasaki R, Kobayashi T, Sato Y, Miyamoto K, Hoshi H, Hashimoto K, Yoshida S, Hao W, Mori T, Kanagawa H, Katsuyama E, Fujie A, Morioka H, Matsumoto M, Chiba K, Takeya M, Toyama Y, Miyamoto T. Osteoclast stimulatory transmembrane protein and dendritic cell-specific transmembrane protein cooperatively modulate cell-cell fusion to form osteoclasts and foreign body giant cells. J Bone Miner Res. 2012;27:1289–97.CrossRefPubMed Miyamoto H, Suzuki T, Miyauchi Y, Iwasaki R, Kobayashi T, Sato Y, Miyamoto K, Hoshi H, Hashimoto K, Yoshida S, Hao W, Mori T, Kanagawa H, Katsuyama E, Fujie A, Morioka H, Matsumoto M, Chiba K, Takeya M, Toyama Y, Miyamoto T. Osteoclast stimulatory transmembrane protein and dendritic cell-specific transmembrane protein cooperatively modulate cell-cell fusion to form osteoclasts and foreign body giant cells. J Bone Miner Res. 2012;27:1289–97.CrossRefPubMed
39.
Zurück zum Zitat Teitelbaum SL. The osteoclast and its unique cytoskeleton. Ann N Y Acad Sci. 2011;1240:14–7.CrossRefPubMed Teitelbaum SL. The osteoclast and its unique cytoskeleton. Ann N Y Acad Sci. 2011;1240:14–7.CrossRefPubMed
41.
Zurück zum Zitat Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O’Brien CA. Matrix-embedded cells control osteoclast formation. Nat Med. 2011;17:1235–41.CrossRefPubMedCentralPubMed Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O’Brien CA. Matrix-embedded cells control osteoclast formation. Nat Med. 2011;17:1235–41.CrossRefPubMedCentralPubMed
42.
Zurück zum Zitat Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, Bonewald LF, Kodama T, Wutz A, Wagner EF, Penninger JM, Takayanagi H. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011;17:1231–4.CrossRefPubMed Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, Bonewald LF, Kodama T, Wutz A, Wagner EF, Penninger JM, Takayanagi H. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011;17:1231–4.CrossRefPubMed
43.
Zurück zum Zitat Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M, Takeshita S, Ikeda K. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007;5:464–75.CrossRefPubMed Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M, Takeshita S, Ikeda K. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007;5:464–75.CrossRefPubMed
44.
Zurück zum Zitat Manolagas SC, Parfitt AM. For whom the bell tolls: distress signals from long-lived osteocytes and the pathogenesis of metabolic bone diseases. Bone. 2013;54:272–8.CrossRefPubMedCentralPubMed Manolagas SC, Parfitt AM. For whom the bell tolls: distress signals from long-lived osteocytes and the pathogenesis of metabolic bone diseases. Bone. 2013;54:272–8.CrossRefPubMedCentralPubMed
46.
Zurück zum Zitat Pederson L, Ruan M, Westendorf JJ, Khosla S, Oursler MJ. Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci U S A. 2008;105:20764–9.CrossRefPubMedCentralPubMed Pederson L, Ruan M, Westendorf JJ, Khosla S, Oursler MJ. Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci U S A. 2008;105:20764–9.CrossRefPubMedCentralPubMed
47.
Zurück zum Zitat Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab. 2006;4:111–21.CrossRefPubMed Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab. 2006;4:111–21.CrossRefPubMed
48.
Zurück zum Zitat Matsuoka K, Park KA, Ito M, Ikeda K, Takeshita S. Osteoclast-derived complement component 3a stimulates osteoblast differentiation. J Bone Miner Res. 2014;29:1522–30.CrossRefPubMed Matsuoka K, Park KA, Ito M, Ikeda K, Takeshita S. Osteoclast-derived complement component 3a stimulates osteoblast differentiation. J Bone Miner Res. 2014;29:1522–30.CrossRefPubMed
51.
Zurück zum Zitat Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res. 2001;16:1575–82.CrossRefPubMed Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res. 2001;16:1575–82.CrossRefPubMed
52.
Zurück zum Zitat Andersen TL, Abdelgawad ME, Kristensen HB, Hauge EM, Rolighed L, Bollerslev J, Kjaersgaard-Andersen P, Delaisse JM. Understanding coupling between bone resorption and formation: are reversal cells the missing link? Am J Pathol. 2013;183:235–46.CrossRefPubMed Andersen TL, Abdelgawad ME, Kristensen HB, Hauge EM, Rolighed L, Bollerslev J, Kjaersgaard-Andersen P, Delaisse JM. Understanding coupling between bone resorption and formation: are reversal cells the missing link? Am J Pathol. 2013;183:235–46.CrossRefPubMed
53.
Zurück zum Zitat Pennypacker BL, Chen CM, Zheng H, Shih MS, Belfast M, Samadfam R, Duong le T. Inhibition of cathepsin k increases modeling-based bone formation, and improves cortical dimension and strength in adult ovariectomized monkeys. J Bone Miner Res. 2014;29:1847–58.CrossRefPubMed Pennypacker BL, Chen CM, Zheng H, Shih MS, Belfast M, Samadfam R, Duong le T. Inhibition of cathepsin k increases modeling-based bone formation, and improves cortical dimension and strength in adult ovariectomized monkeys. J Bone Miner Res. 2014;29:1847–58.CrossRefPubMed
54.
Zurück zum Zitat Jensen PR, Andersen TL, Pennypacker BL, Duong le T, Delaisse JM. The bone resorption inhibitors odanacatib and alendronate affect post-osteoclastic events differently in ovariectomized rabbits. Calcif Tissue Int. 2014;94:212–22.CrossRefPubMedCentralPubMed Jensen PR, Andersen TL, Pennypacker BL, Duong le T, Delaisse JM. The bone resorption inhibitors odanacatib and alendronate affect post-osteoclastic events differently in ovariectomized rabbits. Calcif Tissue Int. 2014;94:212–22.CrossRefPubMedCentralPubMed
55.
Zurück zum Zitat Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ. Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest. 1997;100:1475–80.CrossRefPubMedCentralPubMed Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ. Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest. 1997;100:1475–80.CrossRefPubMedCentralPubMed
56.
Zurück zum Zitat Reid IR, Miller PD, Brown JP, Kendler DL, Fahrleitner-Pammer A, Valter I, Maasalu K, Bolognese MA, Woodson G, Bone H, Ding B, Wagman RB, San Martin J, Ominsky MS, Dempster DW. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res. 2010;25:2256–65.CrossRefPubMed Reid IR, Miller PD, Brown JP, Kendler DL, Fahrleitner-Pammer A, Valter I, Maasalu K, Bolognese MA, Woodson G, Bone H, Ding B, Wagman RB, San Martin J, Ominsky MS, Dempster DW. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res. 2010;25:2256–65.CrossRefPubMed
57.
Zurück zum Zitat Jensen PR, Andersen TL, Pennypacker BL, Duong le T, Engelholm LH, Delaisse JM. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently. Biochem Biophys Res Commun. 2014;443:694–9.CrossRefPubMed Jensen PR, Andersen TL, Pennypacker BL, Duong le T, Engelholm LH, Delaisse JM. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently. Biochem Biophys Res Commun. 2014;443:694–9.CrossRefPubMed
58.
Zurück zum Zitat Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423:337–42.CrossRefPubMed Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423:337–42.CrossRefPubMed
59.
Zurück zum Zitat Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet. 2003;4:638–49.CrossRefPubMed Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet. 2003;4:638–49.CrossRefPubMed
61.
62.
Zurück zum Zitat Edwards JR, Mundy GR. Advances in osteoclast biology: old findings and new insights from mouse models. Nat Rev Rheumatol. 2011;7:235–43.CrossRefPubMed Edwards JR, Mundy GR. Advances in osteoclast biology: old findings and new insights from mouse models. Nat Rev Rheumatol. 2011;7:235–43.CrossRefPubMed
64.
65.
Zurück zum Zitat Redlich K, Smolen JS. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat Rev Drug Discov. 2012;11:234–50.CrossRefPubMed Redlich K, Smolen JS. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat Rev Drug Discov. 2012;11:234–50.CrossRefPubMed
66.
Metadaten
Titel
Molecular and cellular basis of bone resorption
verfasst von
Reinhard Gruber, PhD
Publikationsdatum
01.02.2015
Verlag
Springer Vienna
Erschienen in
Wiener Medizinische Wochenschrift / Ausgabe 3-4/2015
Print ISSN: 0043-5341
Elektronische ISSN: 1563-258X
DOI
https://doi.org/10.1007/s10354-014-0310-0

Weitere Artikel der Ausgabe 3-4/2015

Wiener Medizinische Wochenschrift 3-4/2015 Zur Ausgabe