Receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin system in bone and other tissues (Review)
- Authors:
- Wei Liu
- Xianlong Zhang
-
Affiliations: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China - Published online on: January 7, 2015 https://doi.org/10.3892/mmr.2015.3152
- Pages: 3212-3218
This article is mentioned in:
Abstract
Raggatt LJ and Partridge NC: Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 285:25103–25108. 2010. View Article : Google Scholar : PubMed/NCBI | |
Boyce BF, Xing L, Shakespeare W, Wang Y, Dalgarno D, Iuliucci J and Sawyer T: Regulation of bone remodeling and emerging breakthrough drugs for osteoporosis and osteolytic bone metastases. Kidney Int. 63:S2–S5. 2003. View Article : Google Scholar | |
van Oers RF, Ruimerman R, Tanck E, et al: A unified theory for osteonal and hemi-osteonal remodeling. Bone. 42:250–259. 2008. View Article : Google Scholar | |
Boyce BF and Xing L: Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 473:139–146. 2008. View Article : Google Scholar : PubMed/NCBI | |
Greenfield EM, Bi Y and Miyauchi A: Regulation of osteoclast activity. Life Sci. 65:1087–1102. 1999. View Article : Google Scholar : PubMed/NCBI | |
Lacey D, Timms E, Tan H-L, Kelley M, Dunstan C, Burgess T, Elliott R, Colombero A, Elliott G and Scully S: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 93:165–176. 1998. View Article : Google Scholar : PubMed/NCBI | |
Simonet W, Lacey D, Dunstan C, Kelley M, Chang M-S, Lüthy R, Nguyen H, Wooden S, Bennett L and Boone T: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 89:309–319. 1997. View Article : Google Scholar : PubMed/NCBI | |
Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D and Galibert L: A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 390:175–179. 1997. View Article : Google Scholar : PubMed/NCBI | |
Hanada R, Leibbrandt A, Hanada T, Kitaoka S, Furuyashiki T, Fujihara H, Trichereau J, Paolino M, Qadri F, et al: Central control of fever and female body temperature by RANKL/RANK. Nature. 462:505–509. 2009. View Article : Google Scholar : PubMed/NCBI | |
Karsenty G and Wagner EF: Reaching a genetic and molecular understanding of skeletal development. Dev Cell. 2:389–406. 2002. View Article : Google Scholar : PubMed/NCBI | |
Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S-i, Tomoyasu A, Yano K, Goto M, et al: Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 95:3597–3602. 1998. View Article : Google Scholar : PubMed/NCBI | |
Wong BR, Josien R, Lee SY, et al: 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. 186:2075–2080. 1997. View Article : Google Scholar | |
Rodan GA and Martin TJ: Role of osteoblasts in hormonal control of bone resorption - a hypothesis. Calcif Tissue Int. 33:349–351. 1981. View Article : Google Scholar | |
Yasuda H, Shima N, Nakagawa N, Mochizuki S-I, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K and Kuriyama M: Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology. 139:1329–1337. 1998.PubMed/NCBI | |
Tat SK, Pelletier J-P, Velasco CR, Padrines M and Martel-Pelletier J: New perspective in osteoarthritis: the OPG and RANKL system as a potential therapeutic target? Keio J Med. 58:29–40. 2009. View Article : Google Scholar : PubMed/NCBI | |
Caetano-Lopes J, Canhao H and Fonseca JE: Osteoblasts and bone formation. Acta Reumatol Port. 32:1032007.PubMed/NCBI | |
Boyce BF and Xing L: Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther. 9:S12007. View Article : Google Scholar : PubMed/NCBI | |
Lum L, Wong BR, Josien R, Becherer JD, Erdjument-Bromage H, Schlöndorff J, Tempst P, Choi Y and Blobel CP: Evidence for a role of a tumor necrosis factor-α (TNF-α)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. J Biol Chem. 274:13613–13618. 1999. View Article : Google Scholar : PubMed/NCBI | |
Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FS and Frankel WN: 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. 272:25190–25194. 1997. View Article : Google Scholar : PubMed/NCBI | |
Kong Y-Y, Yoshida H, Sarosi I, Tan H-L, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G and Itie A: OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 397:315–323. 1999. View Article : Google Scholar : PubMed/NCBI | |
Haynes DR, Barg E, Crotti TN, Holding C, Weedon H, Atkins GJ, Zannetino A, Ahern M, Coleman M and Roberts-Thomson PJ: Osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathies and osteoarthritis and normal controls. Rheumatology (Oxford). 42:123–134. 2003. View Article : Google Scholar | |
Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, Tan HL, Elliott G, Kelley MJ and Sarosi I: Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA. 96:3540–3545. 1999. View Article : Google Scholar : PubMed/NCBI | |
Li J, Sarosi I, Yan X-Q, Morony S, Capparelli C, Tan H-L, McCabe S, Elliott R, Scully S and Van G: RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci USA. 97:1566–1571. 2000. View Article : Google Scholar : PubMed/NCBI | |
Galibert L, Tometsko ME, Anderson DM, et al: The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of NF-kappaB, a member of the TNFR superfamily. J Biol Chem. 273:34120–34127. 1998. View Article : Google Scholar : PubMed/NCBI | |
Ye H, Arron JR, Lamothe B, Cirilli M, Kobayashi T, Shevde NK, Segal D, Dzivenu OK, Vologodskaia M, et al: Distinct molecular mechanism for initiating TRAF6 signalling. Nature. 418:443–447. 2002. View Article : Google Scholar : PubMed/NCBI | |
Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K, Takaoka A, Yokochi T, Oda H, et al: T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature. 408:600–605. 2000. View Article : Google Scholar : PubMed/NCBI | |
Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, et al: Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 3:889–901. 2002. View Article : Google Scholar : PubMed/NCBI | |
Kim H-H, Lee DE, Shin JN, Lee YS, Jeon YM, Chung C-H, Ni J, Kwon BS and Lee ZH: Receptor activator of NF-κB recruits multiple TRAF family adaptors and activates c-Jun N-terminal kinase. FEBS Lett. 443:297–302. 1999. View Article : Google Scholar : PubMed/NCBI | |
Darnay BG, Haridas V, Ni J, et al: Characterization of the intracellular domain of receptor activator of NF-kappaB (RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappab and c-Jun N-terminal kinase. J Biol Chem. 273:20551–20555. 1998. View Article : Google Scholar : PubMed/NCBI | |
Naito A, Azuma S, Tanaka S, Miyazaki T, Takaki S, Takatsu K, Nakao K, Nakamura K, Katsuki M and Yamamoto T: Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells. 4:353–362. 1999. View Article : Google Scholar : PubMed/NCBI | |
Lomaga MA, Yeh W-C, Sarosi I, Duncan GS, Furlonger C, Ho A, Morony S, Capparelli C, Van G and Kaufman S: TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev. 13:1015–1024. 1999. View Article : Google Scholar : PubMed/NCBI | |
Wada T, Nakashima T, Oliveira-dos-Santos AJ, Gasser J, Hara H, Schett G and Penninger JM: The molecular scaffold Gab2 is a crucial component of RANK signaling and osteoclastogenesis. Nat Med. 11:394–399. 2005. View Article : Google Scholar : PubMed/NCBI | |
Liu W, Xu D, Yang H, Xu H, Shi Z, Cao X, Takeshita S, Liu J, Teale M and Feng X: Functional identification of three receptor activator of NF-κB cytoplasmic motifs mediating osteoclast differentiation and function. J Biol Chem. 279:54759–54769. 2004. View Article : Google Scholar : PubMed/NCBI | |
Wong BR, Besser D, Kim N, Arron JR, Vologodskaia M, Hanafusa H and Choi Y: TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell. 4:1041–1049. 1999. View Article : Google Scholar | |
Asagiri M, Sato K, Usami T, Ochi S, Nishina H, Yoshida H, Morita I, Wagner EF, Mak TW and Serfling E: Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. J Exp Med. 202:1261–1269. 2005. View Article : Google Scholar : PubMed/NCBI | |
Koga T, Matsui Y, Asagiri M, Kodama T, de Crombrugghe B, Nakashima K and Takayanagi H: NFAT and Osterix cooperatively regulate bone formation. Nat Med. 11:880–885. 2005. View Article : Google Scholar : PubMed/NCBI | |
Theoleyre S, Wittrant Y, Tat SK, Fortun Y, Redini F and Heymann D: The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev. 15:457–475. 2004. View Article : Google Scholar : PubMed/NCBI | |
Bai S, Kopan R, Zou W, Hilton MJ, Ong C-t, Long F, Ross FP and Teitelbaum SL: NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells. J Biol Chem. 283:6509–6518. 2008. View Article : Google Scholar | |
Seeman E and Delmas PD: Bone quality-the material and structural basis of bone strength and fragility. N Engl J Med. 354:2250–2261. 2006. View Article : Google Scholar : PubMed/NCBI | |
Takayanagi H: Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol. 7:292–304. 2007. View Article : Google Scholar : PubMed/NCBI | |
Roodman GD: Cell biology of the osteoclast. Exp Hematol. 27:1229–1241. 1999. View Article : Google Scholar : PubMed/NCBI | |
Walsh MC, Kim N, Kadono Y, et al: Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol. 24:33–63. 2006. View Article : Google Scholar : PubMed/NCBI | |
Takayanagi H: New developments in osteoimmunology. Nat Rev Rheumatol. 8:684–689. 2012. View Article : Google Scholar : PubMed/NCBI | |
Takayanagi H: Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol. 5:667–676. 2009. View Article : Google Scholar : PubMed/NCBI | |
Schroder K, Hertzog PJ, Ravasi T and Hume DA: Interferon-γ: an overview of signals, mechanisms and functions. J Leukoc Biol. 75:163–189. 2004. View Article : Google Scholar | |
Takayanagi H, Kim S, Matsuo K, Suzuki H, Suzuki T, Sato K, Yokochi T, Oda H, Nakamura K and Ida N: RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β. Nature. 416:744–749. 2002. View Article : Google Scholar : PubMed/NCBI | |
Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME and Maliszewski CR: RANK is essential for osteoclast and lymph node development. Genes Dev. 13:2412–2424. 1999. View Article : Google Scholar : PubMed/NCBI | |
Kim D, Mebius RE, MacMicking JD, Jung S, Cupedo T, Castellanos Y, Rho J, Wong BR, Josien R and Kim N: Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE. J Exp Med. 192:1467–1478. 2000. View Article : Google Scholar : PubMed/NCBI | |
Raisz LG: Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. 115:3318–3325. 2005. View Article : Google Scholar : PubMed/NCBI | |
Ghannam NN: Book review: Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Ann Saudi Med. 14:5271994.PubMed/NCBI | |
Ominsky MS, Li X, Asuncion FJ, Barrero M, Warmington KS, Dwyer D, Stolina M, Geng Z, Grisanti M and Tan HL: RANKL inhibition with osteoprotegerin increases bone strength by improving cortical and trabecular bone architecture in ovariectomized rats. J Bone Mine Res. 23:672–682. 2008. View Article : Google Scholar | |
Cummings SR, Martin JS, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M and Wang A: Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 361:756–765. 2009. View Article : Google Scholar : PubMed/NCBI | |
Vega D, Maalouf NM and Sakhaee K: The role of receptor activator of nuclear factor-κB (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab. 92:4514–4521. 2007. View Article : Google Scholar : PubMed/NCBI | |
Pettit A, Walsh N, Manning C, Goldring S and Gravallese E: RANKL protein is expressed at the pannus-bone interface at sites of articular bone erosion in rheumatoid arthritis. Rheumatology (Oxford). 45:1068–1076. 2006. View Article : Google Scholar | |
Ainola M, Mandelin J, Liljestrom M, Konttinen Y and Salo J: Imbalanced expression of RANKL and osteoprotegerin mRNA in pannus tissue of rheumatoid arthritis. Clin Exp Rheumatol. 26:2402008.PubMed/NCBI | |
Haynes D, Crotti T, Weedon H, Slavotinek J, Au V, Coleman M, Roberts-Thomson PJ, Ahern M and Smith MD: Modulation of RANKL and osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis in response to disease-modifying antirheumatic drug treatment and correlation with radiologic outcome. Arthritis Rheum. 59:911–920. 2008. View Article : Google Scholar : PubMed/NCBI | |
Whyte MP, Obrecht SE, Finnegan PM, Jones JL, Podgornik MN, McAlister WH and Mumm S: Osteoprotegerin deficiency and juvenile Paget’s disease. N Engl J Med. 347:175–184. 2002. View Article : Google Scholar : PubMed/NCBI | |
Cundy T, Hegde M, Naot D, Chong B, King A, Wallace R, Mulley J, Love DR, Seidel J and Fawkner M: A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype. Hum Mol Genet. 11:2119–2127. 2002. View Article : Google Scholar : PubMed/NCBI | |
Hughes AE, Ralston SH, Marken J, Bell C, MacPherson H, Wallace RG, van Hul W, Whyte MP, Nakatsuka K and Hovy L: Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. Nat Genet. 24:45–48. 2000. View Article : Google Scholar | |
Sobacchi C, Frattini A, Guerrini MM, Abinun M, Pangrazio A, Susani L, Bredius R, Mancini G, Cant A and Bishop N: Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nat Genet. 39:960–962. 2007. View Article : Google Scholar : PubMed/NCBI | |
Mori K, Le Goff B, Berreur M, Riet A, Moreau A, Blanchard F, Chevalier C, Guisle-Marsollier I, Leger J and Guicheux J: Human osteosarcoma cells express functional receptor activator of nuclear factor-kappa B. J Pathol. 211:555–562. 2007. View Article : Google Scholar : PubMed/NCBI | |
Giuliani N, Colla S, Sala R, Moroni M, Lazzaretti M, La Monica S, Bonomini S, Hojden M, Sammarelli G and Barillè S: Human myeloma cells stimulate the receptor activator of nuclear factor-κB ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. Blood. 100:4615–4621. 2002. View Article : Google Scholar : PubMed/NCBI | |
Mundy GR: Metastasis: Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2:584–593. 2002. View Article : Google Scholar : PubMed/NCBI | |
Weigelt B, Peterse JL and van’t Veer LJ: Breast cancer metastasis: markers and models. Nat Rev Cancer. 5:591–602. 2005. View Article : Google Scholar : PubMed/NCBI | |
Dougall WC and Chaisson M: The RANK/RANKL/OPG triad in cancer-induced bone diseases. Cancer Metastasis Rev. 25:541–549. 2006. View Article : Google Scholar : PubMed/NCBI | |
Fata JE, Kong Y-Y, Li J, Sasaki T, Irie-Sasaki J, Moorehead RA, Elliott R, Scully S, Voura EB and Lacey DL: The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell. 103:41–50. 2000. View Article : Google Scholar : PubMed/NCBI | |
Srivastava S, Matsuda M, Hou Z, Bailey JP, Kitazawa R, Herbst MP and Horseman ND: Receptor activator of NF-κB ligand induction via Jak2 and Stat5a in mammary epithelial cells. J Biol Chem. 278:46171–46178. 2003. View Article : Google Scholar : PubMed/NCBI | |
Cao Y, Bonizzi G, Seagroves TN, Greten FR, Johnson R, Schmidt EV and Karin M: IKKα provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell. 107:763–775. 2001. View Article : Google Scholar : PubMed/NCBI | |
Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Yano K, Morinaga T and Higashio K: RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem Biophys Res Commun. 253:395–400. 1998. View Article : Google Scholar | |
Kartsogiannis V, Zhou H, Horwood N, Thomas R, Hards D, Quinn J, Niforas P, Ng K, Martin T and Gillespie M: Localization of RANKL (receptor activator of NFκB ligand) mRNA and protein in skeletal and extraskeletal tissues. Bone. 25:525–534. 1999. View Article : Google Scholar : PubMed/NCBI | |
Chau D, Becker DL, Coombes ME, et al: Cost-effectiveness of denosumab in the treatment of postmenopausal osteoporosis in Canada. J Med Econ. 15(Suppl 1): 3–14. 2012. View Article : Google Scholar : PubMed/NCBI | |
Dempster DW, Lambing CL, Kostenuik PJ and Grauer A: Role of RANK ligand and denosumab, a targeted RANK ligand inhibitor, in bone health and osteoporosis: a review of preclinical and clinical data. Clin Ther. 34:521–536. 2012. View Article : Google Scholar : PubMed/NCBI | |
Lacey DL, Boyle WJ, Simonet WS, et al: Bench to bedside: elucidation of the OPG–RANK–RANKL pathway and the development of denosumab. Nat Rev Drug Discov. 11:401–419. 2012. View Article : Google Scholar : PubMed/NCBI | |
Lipton A, Fizazi K, Stopeck AT, et al: Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 48:3082–3092. 2012. View Article : Google Scholar : PubMed/NCBI | |
McClung MR, Lewiecki EM, Geller ML, et al: Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial. Osteoporos Int. 24:227–235. 2013. View Article : Google Scholar : |