The RANKL/RANK/OPG pathway

Current Osteoporosis Reports

Volumn 5, Issue 3, 2007, Pages 98-104

  Boyce, Brendan F ^a   Xing, Lianping ^b  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

KILLER CELL ACTIVATING RECEPTOR ASSOCIATED PROTEIN; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; PROTEIN TYROSINE PHOSPHATASE; TRANSCRIPTION FACTOR NFAT; TUMOR NECROSIS FACTOR RECEPTOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 2; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 5; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6;

ALBERS SCHOENBERG DISEASE; BINDING AFFINITY; BONE MARROW; BONE MASS; CELL ACTIVATION; CELL ACTIVITY; CELL MATURATION; NONHUMAN; ONCOGENE C FOS; OSTEOBLAST; OSTEOCLAST; OSTEOLYSIS; REGULATORY MECHANISM; REVIEW;

EID: 35348823325     PISSN: 15441873     EISSN: 15442241     Source Type: Journal    
DOI: 10.1007/s11914-007-0024-y     Document Type: Review

References (50)

1. Rodan GA, Martin TJ: Role of osteoblasts in hormonal control of bone resorption - a hypothesis. Calcif Tissue Int 1981, 33:349-351.
2. Martin TJ, Sims NA: Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med 2005, 11:76-81.
3. Teitelbaum SL, Ross FP: Genetic regulation of osteoclast development and function. Nat Rev Genet 2003, 4:638-649.
4. Black DM, Greenspan SL, Ensrud KE, et al: The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 2003, 349:1207-1215.
5. Ma YL, Bryant HU, Zeng Q, et al.: New bone formation with teriparatide [human parathyroid hormone-(1-34)] is not retarded by long-term pretreatment with alendronate, estrogen, or raloxifene in ovariectomized rats. Endocrinology 2003, 144:2008-2015.
6. 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, 12:1403-1409. This paper shows for the first time that a gene that affects osteoclast fusion also influences osteoblast function in vivo, suggesting that osteoclasts may regulate osteoblast function by producing a soluble factor.
7. Zhao C, Irie N, Takada Y, et al.: Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab 2006, 4:111-121. This study indicates that bidirectional signaling exists between osteoclasts and osteoblasts to maintain bone homeostasis.
8. Simonet WS, Lacey DL, Dunstan CR, et al.: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997, 89:309-319.
9. 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, 139:1329-1337.
10. 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 U S A 1998, 95:3597-3602.
11. Lacey DL, Timms E, Tan HL, et al.: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998, 93:165-176.
12. 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, 390:175-179.
13. Wong BR, Rho J, Arron J, et al.: TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J Biol Chem 1997, 272:25190-25194.
14. American Society for Bone and Mineral Research President's Committee on Nomenclature: Proposed standard nomenclature for new tumor necrosis factor family members involved in the regulation of bone resorption. The American Society for Bone and Mineral Research President's Committee on Nomenclature. J Bone Miner Res 2000, 15:2293-2296.
15. Ikeda T, Kasai M, Utsuyama M, Hirokawa K: Determination of three isoforms of the receptor activator of nuclear factor-κB ligand and their differential expression in bone and thymus. Endocrinology 2001, 142:1419-1426.
16. Lynch CC, Hikosaka A, Acuff HB, et al.: MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell 2005, 7:485-496.
17. Schett G, Hayer S, Zwerina J, et al.: Mechanisms of disease: the link between RANKL and arthritic bone disease. Nat Clin Tract Rheumatol 2005, 1:47-54.
18. Takayanagi H, Kim S, Matsuo K, et al.: RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β. Nature 2002, 416:744-749.
19. Takayanagi H, Ogasawara K, Hida S, et al.: T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 2000, 408:600-605.
20. Takayanagi H: Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 2007, 7:292-304.
21. Feldmann M, Maini RN: Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med 2003, 9:1245-1250.
22. Yao Z, Li P, Zhang Q, et al.: Tumor necrosis factor-α 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, 281:11846-11855. This study demonstrates that TNF increases osteoclast precursor proliferation and differentiation via regulation of c-Fms expression.
23. high osteoclast precursors in tumor necrosis factor α-transgenic mice. Arthritis Rheum 2004, 50:265-276.
24. Kollet O, Dar A, Shivtiel S, et al.: Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nat Med 2006, 12:657-664. First study to show that RANKL not only increases osteoclast function but also stimulates the release of hematopoietic stem cells from the bone marrow. Thus, osteoclasts play a key role in hematopoietic homeostasis.
25. Kim NS, Kim HJ, Koo BK, et al.: Receptor activator of NF-κB ligand regulates the proliferation of mammary epithelial cells via Id2. Mol Cell Biol 2006, 26:1002-1013. The authors demonstrated that mammary epithelial cells express RANK and respond to RANKL treatment. The RANKL/RANK system also regulates mammary gland functions.
26. Fata JE, Kong Y-Y, Li J, et al.: The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell 2000, 103:41-50.
27. Wada T, Nakashima T, Hiroshi N, Penninger JM: RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 2006, 12:17-25.
28. Chen G, Sircar K, Aprikian A, et al.: Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation. Cancer 2006, 107:289-298.
29. Hughes AE, Ralston SH, Marken J, et al.: Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis [letter]. Nat Genet 2000, 24:45-48.
30. Kapur RP, Yao Z, Iida MH, et al.: Malignant autosomal recessive osteopetrosis caused by spontaneous mutation of murine Rank. J Bone Miner Res 2004, 19:1689-1697.
31. Whyte MP, Obrecht SE, Finnegan PM, et al.: Osteoprotegerin deficiency and juvenile Paget's disease. N Engl J Med 2002, 347:175-184.
32. Cundy T, Hegde M, Naot D, et al.: A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype. Hum Mol Genet 2002, 11:2119-2127.
33. Hofbauer LC, Schoppet M: Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 2004, 292:490-495.
34. Boyce BF, Xing L, Chen D: Osteoprotegerin, the bone protector, is a surprising target for beta-catenin signaling. Cell Metab 2005, 2:344-345.
35. Bucay N, Sarosi I, Dunstan CR, et al.: Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998, 12:1260-1268.
36. -/- mice. Arterioscler Thromh Vasc Biol 2006, 26:2117-2124.
37. Collin-Osdoby P: Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ Res 2004, 95:1046-1057.
38. Rogers A, Eastell R: Circulating osteoprotegerin and receptor activator for nuclear factor κB ligand: clinical utility in metabolic bone disease assessment. J Clin Endocrinol Metab 2005, 90:6323-6331.
39. Lomaga MA, Yeh WC, Sarosi I, et al.: TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 1999, 13:1015-1024.
40. 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, 4:353-362.
41. Kurihara N, Hiruma Y, Zhou H, et al.: Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease. J Clin Invest 2007, 117:133-142.
42. 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.
43. -/- mice: novel mechanistic insights from in utero ultrasound biomicroscopy. Circ Res 2004, 95:92-99.
44. Yao Z, Matsuo K, Nishimura R, et al.: c-Fos/NFAT1- or 2-mediated osteoclastogenesis requires NF-κB p50/p52 expression [abstract]. J Bone Miner Res 2005, 20(suppl 1):S145.
45. Asagiri M, Sato K, Usami T, et al.: Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J Exp Med 2005, 202:1261-1269. This study investigated the transcriptional regulation of NFATc1 and revealed that the transcription factors, NF-κB and c-Fos, bind to the NFATc1 promoter in a Temporal fashion and that NFATc1 autoamplifies its expression.
46. Nakashima K, Zhou X, Kunkel G, et al.: The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002, 108:17-29.
47. Koga T, Matsui Y, Asagiri M, et al.: NFAT and osterix cooperatively regulate bone formation. Nat Med 2005, 11:880-885.
48. Thiebaud D, Krieg MA, Gillard-Berguer D, et al.: Cyclosporin induces high bone turnover and may contribute to bone loss after heart transplantation. Eur J Clin Invest 1996, 26:549-555.
49. Koga T, Inui M, Inoue K, et al.: Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature 2004, 428:758-763.
50. Takayanagi H: Mechanistic insight into osteoclast differentiation in osteoimmunology. J Mol Med 2005, 83:170-179.