RESEARCH PROGRESS OF REGULATION OF OSTEOCLAST FORMATION AND FUNCTION_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

 YANYan , LINXin , DAIXiaohua , WANGGuanhua , ZHANGLinpu , ZOUHuiru

Research Center, Stomatological Hospital of Nankai University, Tianjin Stomatological Hospital, Tianjin, 300041, P. R. China;

Corresponding author：

YANYan, Email: magic8502@163.com

Keywords：

Osteoclast; Osteoblast; Bone remodeling; Cytokine; Chemokine

DOI：

10.7507/1002-1892.20140309

Video：

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Objective To review the recent research progress of the regulatory mechanisms of osteoclast (OC) formation and functions. Methods The related literature on OC formation, activation, and functions was reviewed, analyzed, and summarized. Results Macrophage colony stimulating factor and receptor activator of nuclear factor-κB ligand are essential cytokines which regulate all aspects of OC formation and functions. In additional to mediating bone resorption, OCs also partici pate in regulation of osteoblast formation and immune responses. Conclusion The researches on the regulation of OC formation and functions have further revealed the destruction mechanisms of various kinds of bone diseases, which will facil itate to find more suitable biological targets for cl inical therapy.

Citation： YANYan, LINXin, DAIXiaohua, WANGGuanhua, ZHANGLinpu, ZOUHuiru. RESEARCH PROGRESS OF REGULATION OF OSTEOCLAST FORMATION AND FUNCTION. Chinese Journal of Reparative and Reconstructive Surgery, 2014, 28(11): 1435-1440. doi: 10.7507/1002-1892.20140309 Copy

1.	Boyce BF, Zuscik MJ, Xing L. Biology of bone and cartilage//Thakker RV, Whyte MP, Eisman J, et al.Genetics of bone biology and skeletal disease. New York:Elsevier Inc., 2013:3-24.
2.	Boyce BF, Yao Z, Xing L. Osteoclasts have multi ple roles in bone in addition to bone resorption. Crit Rev Eukaryot Gene Exp, 2009, 19(3): 171-180.
3.	Kikuta J, Iwai K, Saeki Y, et al. S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis. Rheumatol Int, 2011, 31(7):967-969.
4.	Lotinun S, Kiviranta R, Matsubara T, et al. Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation. J Clin Invest, 2013, 123(2):666-681.
5.	Aarthi JJ, Darendeliler MA, Pushparaj PN. Dissecting the role of the S1P/S1PR axis in health and disease. J Dent Res, 2011, 90(7):841-854.
6.	Wang Z, McCauley LK. Osteoclasts and odontoclasts:signaling pathways to development and disease. Oral Dis, 2011, 17(2):129-142.
7.	Mellis DJ, Itzstein C, Helfrich MH, et al. The skeleton:a multi-functional complex organ:the role of key signaling pathways in osteoclast differentiation and in bone resorption. J Endocrinol, 2011, 211(2): 131-143.
8.	Xiong J, O'Brien CA. Osteocyte RANKL:new insights into the control of bone remodeling. J Bone Miner Res, 2012, 27(3):499-505.
9.	Boyce BF. Advances in osteoclast biology reveal potential new drug targets and new roles for osteoclasts. J Bone Miner Res, 2013, 28(4):711-722.
10.	Kalyan S, Quabius ES, Wiltfang J, et al. Can peri pheral bloodγδT cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy. J Bone Miner Res, 2013, 28(4):728-735.
11.	DiDonato JA, Mercurio F, Karin M. NF-κB and the link between inflammation and cancer. Immunol Rev, 2012, 246(1):379-400.
12.	Zhao B, Ivashkiv LB. Negative regulation of osteoclastogenesis and bone resorption by cytokines and transcri ptional repressors. Arthritis Res Ther, 2011, 13(4):234.
13.	Chen W, Zhu G, Hao L, et al. C/EBPαregulates osteoclast l ineage commitment. Proc Natl Acad Sci, 2013, 110(18):7294-7299.
14.	Yao Z, Xing L, Boyce BF. NF-κB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism. J Clin Invest, 2009, 119(10):3024-3034.
15.	Jimi E, Aoki K, Saito H, et al. Selective inhibition of NF-κB blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. Nat Med, 2004, 10(6):617-624.
16.	Hemingway F, Taylor R, Knowles HJ, et al. RANKL-independent human osteoclast formation with APRIL, BAFF, NGF, IGF I and IGFⅡ. Bone, 2011, 48(4):938-944.
17.	Teitelbaum SL. The osteoclast and its unique cytoskeleton. Ann N Y Acad Sci, 2011, 1240:14-17.
18.	Eastell R, Nagase S, Ohyama M, et al. Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis:the OCEAN study. J Bone Miner Res, 2011, 26(6):1303-1312.
19.	Leung P, Pickarski M, Zhuo Y, et al. The effects of the cathepsin K inhibitor odanacatib on osteoclastic bone resorption and vesicular trafficking. Bone, 2011, 49(4):623-635.
20.	Stoch SA, Zajic S, Stone JA, et al. Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis:safety, tolerabil ity, pharmacokinetics and pharmacodynamics-results from single oral dose studies in healthy volunteers. Br J Clin Pharmacol, 2013, 75(5):1240-1254.
21.	Tang Y, Wu X, Lei W, et al. TGF-β₁-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med, 2009, 15(7):757-765.
22.	Fujita K, Iwasaki M, Ochi H, et al. Vitamin E decreases bone mass by stimulating osteoclast fusion. Nat Med, 2012, 18(4):589-594.
23.	Takayanagi H. New developments in osteoimmunology. Nat Rev Rheumatol, 2012, 8(11):684-689.
24.	Barrow AD, Raynal N, Andersen TL, et al. OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. J Clin Invest, 2011, 121(9):3505-3516.
25.	Koga T, Matsui Y, Asagiri M, et al. NFAT and Osterix cooperatively regulate bone formation. Nat Med, 2005, 11(8):880-885.
26.	Berthelot JM, Le Goff B. Rheumatoid arthritis and periodontal disease. Joint Bone Spine, 2010, 77(6):537-541.
27.	Schett G, David JP. The multi ple faces of autoimmune-mediated bone loss. Nat Rev Endocrinol, 2010, 6(12):698-706.
28.	Hill TP, Später D, Taketo MM, et al. Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell, 2005, 8(5):727-738.
29.	Maeda K, Kobayashi Y, Udagawa N, et al. Wnt5a-Ror2 signal ing between osteoblast-l ineage cells and osteoclast precursors enhances osteoclastogenesis. Nature medicine, 2012, 18(3):405-412.
30.	Kang S, Kumanogoh A. Semaphorins in bone development, homeostasis, and disease. Semin Cell Dev Biol, 2013, 24(3):163-171.
31.	Zhao C, Irie N, Takada Y, et al. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab, 2006, 4(2):111-121.
32.	Miyauchi Y, Ninomiya K, Miyamoto H, et al. The Blimp1-Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis. J Exp Med, 2010, 207(4):751-762.
33.	Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factorκB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev, 2008, 29(2):155-192.
34.	Mahoney DJ, Swales C, Athanasou NA, et al. TSG-6 inhibits osteoclast activity via an autocrine mechanism and is functionally synergistic with osteoprotegerin. Arthritis Rheum, 2011, 63(4):1034-1043.
35.	Nakamura T, Imai Y, Matsumoto T, et al. Estrogen prevents bone loss via estrogen receptorαand induction of Fas ligand in osteoclasts. Cell, 2007, 130(5):811-823.
36.	Rogers MJ, Crockett JC, Coxon FP, et al. Biochemical and molecular mechanisms of action of bisphosphonates. Bone, 2011, 49(1):34-41.
37.	Hanley DA, Adachi JD, Bell A, et al. Denosumab:mechanism of action and cl inical outcomes. Int J Clin Pract, 2012, 66(12):1139-1146.
38.	Boonen S, Rosenberg E, Claessens F, et al. Inhibition of cathepsin K for treatment of osteoporosis. Curr Osteoporos Rep, 2012, 10(1):73-79.
39.	Tanaka S, Wakeyama H, Akiyama T, et al. Regulation of osteoclast apoptosis by bcl-2 family protein Bim and Caspase-3. Adv Exp Med Biol, 2010, 658:111-116.

1. Boyce BF, Zuscik MJ, Xing L. Biology of bone and cartilage//Thakker RV, Whyte MP, Eisman J, et al.Genetics of bone biology and skeletal disease. New York:Elsevier Inc., 2013:3-24.
2. Boyce BF, Yao Z, Xing L. Osteoclasts have multi ple roles in bone in addition to bone resorption. Crit Rev Eukaryot Gene Exp, 2009, 19(3): 171-180.
3. Kikuta J, Iwai K, Saeki Y, et al. S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis. Rheumatol Int, 2011, 31(7):967-969.
4. Lotinun S, Kiviranta R, Matsubara T, et al. Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation. J Clin Invest, 2013, 123(2):666-681.
5. Aarthi JJ, Darendeliler MA, Pushparaj PN. Dissecting the role of the S1P/S1PR axis in health and disease. J Dent Res, 2011, 90(7):841-854.
6. Wang Z, McCauley LK. Osteoclasts and odontoclasts:signaling pathways to development and disease. Oral Dis, 2011, 17(2):129-142.
7. Mellis DJ, Itzstein C, Helfrich MH, et al. The skeleton:a multi-functional complex organ:the role of key signaling pathways in osteoclast differentiation and in bone resorption. J Endocrinol, 2011, 211(2): 131-143.
8. Xiong J, O'Brien CA. Osteocyte RANKL:new insights into the control of bone remodeling. J Bone Miner Res, 2012, 27(3):499-505.
9. Boyce BF. Advances in osteoclast biology reveal potential new drug targets and new roles for osteoclasts. J Bone Miner Res, 2013, 28(4):711-722.
10. Kalyan S, Quabius ES, Wiltfang J, et al. Can peri pheral bloodγδT cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy. J Bone Miner Res, 2013, 28(4):728-735.
11. DiDonato JA, Mercurio F, Karin M. NF-κB and the link between inflammation and cancer. Immunol Rev, 2012, 246(1):379-400.
12. Zhao B, Ivashkiv LB. Negative regulation of osteoclastogenesis and bone resorption by cytokines and transcri ptional repressors. Arthritis Res Ther, 2011, 13(4):234.
13. Chen W, Zhu G, Hao L, et al. C/EBPαregulates osteoclast l ineage commitment. Proc Natl Acad Sci, 2013, 110(18):7294-7299.
14. Yao Z, Xing L, Boyce BF. NF-κB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism. J Clin Invest, 2009, 119(10):3024-3034.
15. Jimi E, Aoki K, Saito H, et al. Selective inhibition of NF-κB blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. Nat Med, 2004, 10(6):617-624.
16. Hemingway F, Taylor R, Knowles HJ, et al. RANKL-independent human osteoclast formation with APRIL, BAFF, NGF, IGF I and IGFⅡ. Bone, 2011, 48(4):938-944.
17. Teitelbaum SL. The osteoclast and its unique cytoskeleton. Ann N Y Acad Sci, 2011, 1240:14-17.
18. Eastell R, Nagase S, Ohyama M, et al. Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis:the OCEAN study. J Bone Miner Res, 2011, 26(6):1303-1312.
19. Leung P, Pickarski M, Zhuo Y, et al. The effects of the cathepsin K inhibitor odanacatib on osteoclastic bone resorption and vesicular trafficking. Bone, 2011, 49(4):623-635.
20. Stoch SA, Zajic S, Stone JA, et al. Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis:safety, tolerabil ity, pharmacokinetics and pharmacodynamics-results from single oral dose studies in healthy volunteers. Br J Clin Pharmacol, 2013, 75(5):1240-1254.
21. Tang Y, Wu X, Lei W, et al. TGF-β₁-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med, 2009, 15(7):757-765.
22. Fujita K, Iwasaki M, Ochi H, et al. Vitamin E decreases bone mass by stimulating osteoclast fusion. Nat Med, 2012, 18(4):589-594.
23. Takayanagi H. New developments in osteoimmunology. Nat Rev Rheumatol, 2012, 8(11):684-689.
24. Barrow AD, Raynal N, Andersen TL, et al. OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. J Clin Invest, 2011, 121(9):3505-3516.
25. Koga T, Matsui Y, Asagiri M, et al. NFAT and Osterix cooperatively regulate bone formation. Nat Med, 2005, 11(8):880-885.
26. Berthelot JM, Le Goff B. Rheumatoid arthritis and periodontal disease. Joint Bone Spine, 2010, 77(6):537-541.
27. Schett G, David JP. The multi ple faces of autoimmune-mediated bone loss. Nat Rev Endocrinol, 2010, 6(12):698-706.
28. Hill TP, Später D, Taketo MM, et al. Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell, 2005, 8(5):727-738.
29. Maeda K, Kobayashi Y, Udagawa N, et al. Wnt5a-Ror2 signal ing between osteoblast-l ineage cells and osteoclast precursors enhances osteoclastogenesis. Nature medicine, 2012, 18(3):405-412.
30. Kang S, Kumanogoh A. Semaphorins in bone development, homeostasis, and disease. Semin Cell Dev Biol, 2013, 24(3):163-171.
31. Zhao C, Irie N, Takada Y, et al. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab, 2006, 4(2):111-121.
32. Miyauchi Y, Ninomiya K, Miyamoto H, et al. The Blimp1-Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis. J Exp Med, 2010, 207(4):751-762.
33. Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factorκB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev, 2008, 29(2):155-192.
34. Mahoney DJ, Swales C, Athanasou NA, et al. TSG-6 inhibits osteoclast activity via an autocrine mechanism and is functionally synergistic with osteoprotegerin. Arthritis Rheum, 2011, 63(4):1034-1043.
35. Nakamura T, Imai Y, Matsumoto T, et al. Estrogen prevents bone loss via estrogen receptorαand induction of Fas ligand in osteoclasts. Cell, 2007, 130(5):811-823.
36. Rogers MJ, Crockett JC, Coxon FP, et al. Biochemical and molecular mechanisms of action of bisphosphonates. Bone, 2011, 49(1):34-41.
37. Hanley DA, Adachi JD, Bell A, et al. Denosumab:mechanism of action and cl inical outcomes. Int J Clin Pract, 2012, 66(12):1139-1146.
38. Boonen S, Rosenberg E, Claessens F, et al. Inhibition of cathepsin K for treatment of osteoporosis. Curr Osteoporos Rep, 2012, 10(1):73-79.
39. Tanaka S, Wakeyama H, Akiyama T, et al. Regulation of osteoclast apoptosis by bcl-2 family protein Bim and Caspase-3. Adv Exp Med Biol, 2010, 658:111-116.

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