Therapeutic targeting of osteoclast function and pathways

Expert Opinion on Therapeutic Targets

Volumn 15, Issue 2, 2011, Pages 169-181

  Broadhead, Matthew L ^a   Clark, Jonathan C ^a   Dass, Crispin R ^b   Choong, Peter F ^a,c   Myers, Damian E ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b VICTORIA UNIVERSITY   (Australia)

^c PETER MACCALLUM CANCER CENTRE   (Australia)

Author keywords

bone metastases; osteoclast; osteoporosis; osteosarcoma; rheumatoid arthritis

Indexed keywords

BISPHOSPHONIC ACID DERIVATIVE; COLONY STIMULATING FACTOR 1; DENOSUMAB; DISEASE MODIFYING ANTIRHEUMATIC DRUG; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLIXIMAB; OSTEOCLAST DIFFERENTIATION FACTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RALOXIFENE; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR NFATC1; UNCLASSIFIED DRUG;

BONE CANCER; CELL DIFFERENTIATION; CELL FUNCTION; GIANT CELL TUMOR; INTRACELLULAR SIGNALING; MOLECULAR BIOLOGY; MOLECULAR IMAGING; MOLECULAR MECHANICS; OSTEOCLAST; OSTEOCLASTOGENESIS; OSTEOLYSIS; OSTEOPOROSIS; OSTEOSARCOMA; PATIENT MONITORING; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; SRC HOMOLOGY DOMAIN;

BONE AND BONES; BONE NEOPLASMS; BONE RESORPTION; CELL DIFFERENTIATION; HUMANS; MACROPHAGE COLONY-STIMULATING FACTOR; MOLECULAR TARGETED THERAPY; OSTEOCLASTS; OSTEOPOROSIS; RANK LIGAND; SIGNAL TRANSDUCTION;

EID: 78651367559     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.2011.546351     Document Type: Review

References (110)

1. Lerner UH. Bone remodeling in post-menopausal osteoporosis. J Dent Res 2006;85:584-95
2. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337-42
3. Miyamoto T, Suda T. Differentiation and function of osteoclasts. Keio J Med 2003;52:1-7
4. Ash P, Loutit JF, Townsend KM. Osteoclasts derived from haematopoietic stem cells. Nature 1980;283:669-70
5. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7
6. Takahashi N, Yamana H, Yoshiki S, et al. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology 1988;122:1373-82
7. Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93:165-76
8. Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/ osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 1998;95:3597-602
9. Yavropoulou MP, Yovos JG. Osteoclastogenesis-current knowledge and future perspectives. J Musculoskelet Neuronal Interact 2008;8:204-16
10. Lerner UH. Osteoclast formation and resorption. Matrix Biol 2000;19:107-20
11. Nakagawa N, Kinosaki M, Yamaguchi K, et al. RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem Biophys Res Commun 1998;253:395-400
12. Hsu H, Lacey DL, Dunstan CR, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA 1999;96:3540-5
13. Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997;89:309-19
14. Tsuda E, Goto M, Mochizuki S, et al. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Commun 1997;234:137-42
15. Whyte MP, Obrecht SE, Finnegan PM, et al. Osteoprotegerin deficiency and juvenile Pagets disease. N Engl J Med 2002;347:175-84
16. Hughes AE, Ralston SH, Marken J, et al. Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. Nat Genet 2000;24:45-8
17. Nakatsuka K, Nishizawa Y, Ralston SH. Phenotypic characterization of early onset Pagets disease of bone caused by a 27-bp duplication in the TNFRSF11A gene. J Bone Miner Res 2003;18:1381-5
18. Yasuda H, Shima N, Nakagawa N, et al. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 1998;139:1329-37
19. Anderson DM, Maraskovsky E, Billingsley WL, et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 1997;390:175-9
20. Baron R, Neff L, Tran Van P, et al. Kinetic and cytochemical identification of osteoclast precursors and their differentiation into multinucleated osteoclasts. Am J Pathol 1986;122:363-78
21. Yagi M, Miyamoto T, Sawatani Y, et al. DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. J Exp Med 2005;202:345-51
22. Lee SH, Rho J, Jeong D, et al. v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation. Nat Med 2006;12:1403-9
23. Yao Z, Li P, Zhang Q, et al. Tumor necrosis factor-alpha increases circulating osteoclast precursor numbers by promoting their proliferation and differentiation in the bone marrow through up-regulation of c-Fms expression. J Biol Chem 2006;281:11846-55
24. Weir EC, Lowik CW, Paliwal I, et al. Colony stimulating factor-1 plays a role in osteoclast formation and function in bone resorption induced by parathyroid hormone and parathyroid hormone-related protein. J Bone Miner Res 1996;11:1474-81
25. Alberts B, Johnson A, Lewis J, et al. Molecular biology of the cell. 5th edition: Garland Science, New York; 2008
26. Ross FP. M-CSF, c-Fms, and signaling in osteoclasts and their precursors. Ann N Y Acad Sci 2006;1068:110-16
27. Naito A, Azuma S, Tanaka S, et al. Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 1999;4:353-62
28. Inoue J, Ishida T, Tsukamoto N, et al. Tumor necrosis factor receptor-associated factor (TRAF) family: adapter proteins that mediate cytokine signaling. Exp Cell Res 2000;254:14-24
29. Kobayashi N, Kadono Y, Naito A, et al. Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis. EMBO J 2001;20:1271-80
30. Akiyama T, Dass CR, Choong PF. Novel therapeutic strategy for osteosarcoma targeting osteoclast differentiation, bone-resorbing activity, and apoptosis pathway. Mol Cancer Ther 2008;7:3461-9
31. Wada T, Nakashima T, Oliveira-dos- Santos AJ, et al. The molecular scaffold Gab2 is a crucial component of RANK signaling and osteoclastogenesis. Nat Med 2005;11:394-9
32. Negishi-Koga T, Takayanagi H. Ca2+-NFATc1 signaling is an essentialaxis of osteoclast differentiation. Immunol Rev 2009;231:241-56
33. + accelerates nuclear translocation of nuclear factor kappaB in osteoclasts. J Biol Chem 2003;278:8286-93
34. Soysa NS, Alles N. NF-kappaB functions in osteoclasts. Biochem Biophys Res Commun 2009;378:1-5
35. Dejardin E. The alternative NF-kappaB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochem Pharmacol 2006;72:1161-79
36. Iotsova V, Caamano J, Loy J, et al. Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat Med 1997;3:1285-9
37. Ruocco MG, Maeda S, Park JM, et al. IkappaB kinase (IKK)beta, but not IKKkappa, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss. J Exp Med 2005;201:1677-87
38. Wong BR, Besser D, Kim N, et al. TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell 1999;4:1041-9
39. Takeshita S, Namba N, Zhao JJ, et al. SHIP-deficient mice are severely osteoporotic due to increased numbers of hyper-resorptive osteoclasts. Nat Med 2002;8:943-9
40. Ishida N, Hayashi K, Hoshijima M, et al. Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator. J Biol Chem 2002;277:41147-56
41. Takayanagi H, Kim S, Koga T, et al. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 2002;3:889-901
42. Asagiri M, Sato K, Usami T, et al. Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J Exp Med 2005;202:1261-9
43. Matsuo K, Galson DL, Zhao C, et al. Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. J Biol Chem 2004;279:26475-80
44. Koga T, Matsui Y, Asagiri M, et al. NFAT and Osterix cooperatively regulate bone formation. Nat Med 2005;11:880-5
45. Duong LT, Lakkakorpi P, Nakamura I, et al. Integrins and signaling in osteoclast function. Matrix Biol 2000;19:97-105
46. Miyauchi A, Alvarez J, Greenfield EM, et al. Recognition of osteopontin and related peptides by an alphav beta3 integrin stimulates immediate cell signals in osteoclasts. J Biol Chem 1991;266:20369-74
47. Proff P, Romer P. The molecular mechanism behind bone remodelling: a review. Clin Oral Investig 2009;13:355-62
48. Vaananen HK, Laitala-Leinonen T. Osteoclast lineage and function. Arch Biochem Biophys 2008;473:132-8
49. Saftig P, Hunziker E, Everts V, et al. Functions of cathepsin K in bone resorption. Lessons from cathepsin K deficient mice. Adv Exp Med Biol 2000;477:293-303
50. Li YP, Chen W, Liang Y, et al. Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification. Nat Genet 1999;23:447-51
51. Nesbitt SA, Horton MA. Trafficking of matrix collagens through bone-resorbing osteoclasts. Science 1997;276:266-9
52. Datta HK, MacIntyre I, Zaidi M. The effect of extracellular calcium elevation on morphology and function of isolated rat osteoclasts. Biosci Rep 1989;9:747-51
53. Lorget F, Kamel S, Mentaverri R, et al. High extracellular calcium concentrations directly stimulate osteoclast apoptosis. Biochem Biophys Res Commun 2000;268:899-903
54. Yamaguchi T. The calcium-sensing receptor in bone. J Bone Miner Metab 2008;26:301-11
55. Udagawa N, Takahashi N, Yasuda H, et al. Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology 2000;141:3478-84
56. Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 2002;22:549-53
57. Kumar V, Abbas A, Fausto N. Robbins and Cotran pathologic basis of disease. 7th edition. Elsevier Saunders, Philadelphia; 2005
58. Halasy-Nagy JM, Rodan GA, Reszka AA. Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis. Bone 2001;29:553-9
59. Weinstein RS, Roberson PK, Manolagas SC. Giant osteoclast formation and long-term oral bisphosphonate therapy. N Engl J Med 2009;360:53-62
60. Stresing V, Daubine F, Benzaid I, et al. Bisphosphonates in cancer therapy. Cancer Lett 2007;257:16-35
61. Ory B, Blanchard F, Battaglia S, et al. Zoledronic acid activates the DNA S-phase checkpoint and induces osteosarcoma cell death characterized by apoptosis-inducing factor and endonuclease-G translocation independently of p53 and retinoblastoma status. Mol Pharmacol 2007;71:333-43
62. Osteoporosis [revised June 2009]. In: eTG complete [Internet]. Melbourne: Therapeutic Guidelines Limited; March 2010. Accessed 16 October 2010
63. Hill DA, Hill SR. Counseling patients about hormone therapy and alternatives for menopausal symptoms. Am Fam Physician 2010;82:801-7
64. Nelson HD. Hormone Replacement Therapy and Osteoporosis. Systematic Evidence Reviews, No. 12. Portland, Oregon: Agency for Healthcare Research and Quality (US) 2002. Available from: http://www.ncbi.nlm.nih.gov/books/NBK42693/ [Last accessed 9 December 2010]
65. Karmakar S, Kay J, Gravallese EM. Bone damage in rheumatoid arthritis: mechanistic insights and approaches to prevention. Rheum Dis Clin North Am 2010;36:385-404
66. Pettit AR, Ji H, von Stechow D, et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol 2001;159:1689-99
67. Redlich K, Hayer S, Ricci R, et al. Osteoclasts are essential for TNF-alpha-mediated joint destruction. J Clin Invest 2002;110:1419-27
68. Van bezooijen RL, Farih-Sips HC, Papapoulos SE, et al. Interleukin-17:a new bone acting cytokine in vitro. J Bone Miner Res 1999;14:1513-21
69. Van Bezooijen RL, Papapoulos SE, Lowik CW. Effect of interleukin-17 on nitric oxide production and osteoclastic bone resorption: is there dependency on nuclear factor-kappaB and receptor activator of nuclear factor kappaB (RANK)/RANK ligand signaling? Bone 2001;28:378-86
70. Sato K, Suematsu A, Okamoto K, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 2006;203:2673-82
71. Lubberts E, van den Bersselaar L, Oppers-Walgreen B, et al. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappaB ligand/osteoprotegerin balance. J Immunol 2003;170:2655-62
72. Haynes DR, Crotti TN, Loric M, et al. Osteoprotegerin and receptor activator of nuclear factor kappaB ligand (RANKL) regulate osteoclast formation by cells in the human rheumatoid arthritic joint. Rheumatology (Oxford) 2001;40:623-30
73. Kong YY, Feige U, Sarosi I, et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 1999;402:304-9
74. Herrak P, Gortz B, Hayer S, et al. Zoledronic acid protects against local and systemic bone loss in tumor necrosis factor-mediated arthritis. Arthritis Rheum 2004;50:2327-37
75. Daoussis D, Andonopoulos AP, Liossis SN. Wnt pathway and IL-17: novel regulators of joint remodeling in rheumatic diseases. Looking beyond the RANK-RANKL-OPG axis. Semin Arthritis Rheum 2010;39:369-83
76. Gengenbacher M, Sebald HJ, Villiger PM, et al. Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis 2008;67:620-4
77. Seriolo B, Paolino S, Sulli A, et al. Bone metabolism changes during anti-TNF-alpha therapy in patients with active rheumatoid arthritis. Ann N Y Acad Sci 2006;1069:420-7
78. Chopin F, Garnero P, le Henanff A, et al. Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis. Ann Rheum Dis 2008;67:353-7
79. Cohen SB, Dore RK, Lane NE, et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, Phase II clinical trial. Arthritis Rheum 2008;58:1299-309
80. Dore RK, Cohen SB, Lane NE, et al. Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis 2010;69:872-5
81. Sharp JT, Tsuji W, Ory P, et al. Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis. Arthritis Care Res (Hoboken) 2010;62:537-44
82. Deodhar A, Dore RK, Mandel D, et al. Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients. Arthritis Care Res (Hoboken) 2010;62:569-74
83. Guise TA, Chirgwin JM. Transforming growth factor-beta in osteolytic breast cancer bone metastases. Clin Orthop Relat Res 2003;(415 Suppl):S32-8
84. Kinpara K, Mogi M, Kuzushima M, et al. Osteoclast differentiation factor in human osteosarcoma cell line. J Immunoassay 2000;21:327-40
85. Wood J, Bonjean K, Ruetz S, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 2002;302:1055-61
86. Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest 2004;114:623-33
87. Soltau J, Zirrgiebel U, Esser N, et al. Antitumoral and antiangiogenic efficacy of bisphosphonates in vitro and in a murine RENCA model. Anticancer Res 2008;28(2A):933-41
88. Stearns ME. Alendronate blocks TGF-beta1 stimulated collagen 1 degradation by human prostate PC-3 ML cells. Clin Exp Metastasis 1998;16:332-9
89. Lai TJ, Hsu SF, Li TM, et al. Alendronate inhibits cell invasion and MMP-2 secretion in human chondrosarcoma cell line. Acta Pharmacol Sin 2007;28:1231-5
90. Cheng YY, Huang L, Lee KM, et al. Alendronate regulates cell invasion and MMP-2 secretion in human osteosarcoma cell lines. Pediatr Blood Cancer 2004;42:410-15
91. Coleman RE. Optimising treatment of bone metastases by ArediaTM and ZometaTM. Breast Cancer 2000;7:361-9
92. Zhang J, Dai J, Yao Z, et al. Soluble receptor activator of nuclear factor kappaB Fc diminishes prostate cancer progression in bone. Cancer Res 2003;63:7883-90
93. Oyajobi BO, Anderson DM, Traianedes K, et al. Therapeutic efficacy of a soluble receptor activator of nuclear factor kappaB-IgG Fc fusion protein in suppressing bone resorption and hypercalcemia in a model of humoral hypercalcemia of malignancy. Cancer Res 2001;61:2572-8
94. Zhang J, Dai J, Qi Y, et al. Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. J Clin Invest 2001;107:1235-44
95. Holen I, Croucher PI, Hamdy FC, et al. Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells. Cancer Res 2002;62:1619-23
96. Morony S, Capparelli C, Sarosi I, et al. Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis. Cancer Res 2001;61:4432-6
97. Croucher PI, Shipman CM, Lippitt J, et al. Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 2001;98:3534-40
98. Honore P, Luger NM, Sabino MA, et al. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-relatedneurochemical reorganization of the spinal cord. Nat Med 2000;6:521-8
99. Luger NM, Honore P, Sabino MA, et al. Osteoprotegerin diminishes advanced bone cancer pain. Cancer Res 2001;61:4038-47
100. Canon JR, Roudier M, Bryant R, et al. Inhibition of RANKL blocks skeletal tumor progression and improves survival in a mouse model of breast cancer bone metastasis. Clin Exp Metastasis 2008;25:119-29
101. Green LL. Antibody engineering via genetic engineering of the mouse: XenoMouse strains are a vehicle for the facile generation of therapeutic human monoclonal antibodies. J Immunol Methods 1999;231:11-23
102. Schwarz EM, Ritchlin CT. Clinical development of anti-RANKL therapy. Arthritis Res Ther 2007;9(Suppl 1):S7
103. Lipton A, Steger GG, Figueroa J, et al. Randomized active-controlled Phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 2007;25:4431-7
104. Yonemori K, Fujiwara Y, Minami H, et al. Phase 1 trial of denosumab safety, pharmacokinetics, and pharmacodynamics in Japanese women with breast cancer-related bone metastases. Cancer Sci 2008;99:1237-42
105. Body JJ, Facon T, Coleman RE, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 2006;12:1221-8
106. Lamoureux F, Richard P, Wittrant Y, et al. Therapeutic relevance of osteoprotegerin gene therapy in osteosarcoma: blockade of the vicious cycle between tumor cell proliferation and bone resorption. Cancer Res 2007;67:7308-73018
107. Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol 2010;11:275-80
108. Morgan T, Atkins GJ, Trivett MK, et al. Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB. Am J Pathol 2005;167:117-28
109. Kyrgidis A, Toulis K. Safety and efficacy of denosumab in giant-cell tumour of bone. Lancet Oncol 2010;11:513-14
110. Thomas D, Carriere P, Jacobs I. Safety of denosumab in giant-cell tumour of bone. Lancet Oncol 2010;11:815