RANKL as the master regulator of osteoclast differentiation

Okamoto K, Nakashima T, Shinohara M, Negishi-Koga T, Komatsu N, Terashima A, Sawa S, Nitta T, Takayanagi H (2017) Osteoimmunology: the conceptual framework unifying the immune and skeletal systems (in eng). Physiol Rev 97:1295–1349. https://doi.org/10.1152/physrev.00036.2016 Tsukasaki M, Takayanagi H (2019) Osteoimmunology: evolving concepts in bone-immune interactions in health and disease (in eng). Nat Rev Immunol 19:626–642. https://doi.org/10.1038/s41577-019-0178-8 Asagiri M, Takayanagi H (2007) The molecular understanding of osteoclast differentiation (in eng). Bone 40:251–264. https://doi.org/10.1016/j.bone.2006.09.023 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 (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL (in eng). Proc Natl Acad Sci U S A 95:3597–3602 Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation (in eng). Cell 93:165–176 Tsukasaki M, Hamada K, Okamoto K, Nagashima K, Terashima A, Komatsu N, Win SJ, Okamura T, Nitta T, Yasuda H, Penninger JM, Takayanagi H (2017) LOX fails to substitute for RANKL in osteoclastogenesis (in eng). J Bone Miner Res 32:434–439. https://doi.org/10.1002/jbmr.2990 Tanaka S (2017) RANKL-independent osteoclastogenesis: a long-standing controversy (in eng). J Bone Miner Res 32:431–433. https://doi.org/10.1002/jbmr.3092 Teitelbaum SL, Ross FP (2003) Genetic regulation of osteoclast development and function (in eng). Nat Rev Genet 4:638–649. https://doi.org/10.1038/nrg1122 Tolar J, Teitelbaum SL, Orchard PJ (2004) Osteopetrosis (in eng). N Engl J Med 351:2839–2849. https://doi.org/10.1056/NEJMra040952 Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S (1993) Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death (in eng). Proc Natl Acad Sci U S A 90:770–774. https://doi.org/10.1073/pnas.90.2.770 Vargas SJ, Naprta A, Glaccum M, Lee SK, Kalinowski J, Lorenzo JA (1996) Interleukin-6 expression and histomorphometry of bones from mice deficient in receptors for interleukin-1 or tumor necrosis factor (in eng). J Bone Miner Res 11:1736–1744. https://doi.org/10.1002/jbmr.5650111117 Wiktor-Jedrzejczak W, Bartocci A, Ferrante AW, Ahmed-Ansari A, Sell KW, Pollard JW, Stanley ER (1990) Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse (in eng). Proc Natl Acad Sci U S A 87:4828–4832. https://doi.org/10.1073/pnas.87.12.4828 Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, Sudo T, Shultz LD (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene (in eng). Nature 345:442–444. https://doi.org/10.1038/345442a0 Nakamichi Y, Mizoguchi T, Arai A, Kobayashi Y, Sato M, Penninger JM, Yasuda H, Kato S, DeLuca HF, Suda T, Udagawa N, Takahashi N (2012) Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice (in eng). Proc Natl Acad Sci U S A 109:10006–10011. https://doi.org/10.1073/pnas.1207361109 Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis (in eng). Nature 397:315–323. https://doi.org/10.1038/16852 Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR, Armstrong A, Shen V, Bain S, Cosman D, Anderson D, Morrissey PJ, Peschon JJ, Schuh J (1999) RANK is essential for osteoclast and lymph node development (in eng). Genes Dev 13:2412–2424 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 (2011) Evidence for osteocyte regulation of bone homeostasis through RANKL expression (in eng). Nat Med 17:1231–1234. https://doi.org/10.1038/nm.2452 Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O’Brien CA (2011) Matrix-embedded cells control osteoclast formation (in eng). Nat Med 17:1235–1241. https://doi.org/10.1038/nm.2448 Sobacchi C, Frattini A, Guerrini MM, Abinun M, Pangrazio A et al (2007) Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL (in eng). Nat Genet 39:960–962. https://doi.org/10.1038/ng2076 Guerrini MM, Sobacchi C, Cassani B, Abinun M, Kilic SS et al (2008) Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations (in eng). Am J Hum Genet 83:64–76. https://doi.org/10.1016/j.ajhg.2008.06.015 Tsukasaki M, Asano T, Muro R, Huynh NC, Komatsu N, Okamoto K, Nakano K, Okamura T, Nitta T, Takayanagi H (2020) OPG production matters where it happened (in eng). Cell Rep 32:108124. https://doi.org/10.1016/j.celrep.2020.108124 Cawley KM, Bustamante-Gomez NC, Guha AG, MacLeod RS, Xiong J, Gubrij I, Liu Y, Mulkey R, Palmieri M, Thostenson JD, Goellner JJ, O’Brien CA (2020) Local production of osteoprotegerin by osteoblasts suppresses bone resorption (in eng). Cell Rep 32:108052. https://doi.org/10.1016/j.celrep.2020.108052 Li J, Sarosi I, Yan XQ, Morony S, Capparelli C et al (2000) RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism (in eng). Proc Natl Acad Sci U S A 97:1566–1571 O’Brien W, Fissel BM, Maeda Y, Yan J, Ge X, Gravallese EM, Aliprantis AO, Charles JF (2016) RANK-independent osteoclast formation and bone erosion in inflammatory arthritis (in eng). Arthritis Rheumatol 68:2889–2900. https://doi.org/10.1002/art.39837 Pettit AR, Ji H, von Stechow D, Müller R, Goldring SR, Choi Y, Benoist C, Gravallese EM (2001) TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis (in eng). Am J Pathol 159:1689–1699. https://doi.org/10.1016/S0002-9440(10)63016-7 Danks L, Komatsu N, Guerrini MM, Sawa S, Armaka M, Kollias G, Nakashima T, Takayanagi H (2016) RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation (in eng). Ann Rheum Dis 75:1187–1195. https://doi.org/10.1136/annrheumdis-2014-207137 Tsukasaki M, Komatsu N, Nagashima K, Nitta T, Pluemsakunthai W, Shukunami C, Iwakura Y, Nakashima T, Okamoto K, Takayanagi H (2018) Host defense against oral microbiota by bone-damaging T cells (in eng). Nat Commun 9:701. https://doi.org/10.1038/s41467-018-03147-6 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 (2004) Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis (in eng). Nature 428:758–763. https://doi.org/10.1038/nature02444 Negishi-Koga T, Gober HJ, Sumiya E, Komatsu N, Okamoto K, Sawa S, Suematsu A, Suda T, Sato K, Takai T, Takayanagi H (2015) Immune complexes regulate bone metabolism through FcRγ signalling (in eng). Nat Commun 6:6637. https://doi.org/10.1038/ncomms7637 Shinohara M, Koga T, Okamoto K, Sakaguchi S, Arai K, Yasuda H, Takai T, Kodama T, Morio T, Geha RS, Kitamura D, Kurosaki T, Ellmeier W, Takayanagi H (2008) Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals (in eng). Cell 132:794–806. https://doi.org/10.1016/j.cell.2007.12.037 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 (2002) Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts (in eng). Dev Cell 3:889–901 Asagiri M, Sato K, Usami T, Ochi S, Nishina H, Yoshida H, Morita I, Wagner EF, Mak TW, Serfling E, Takayanagi H (2005) Autoamplification of NFATc1 expression determines its essential role in bone homeostasis (in eng). J Exp Med 202:1261–1269. https://doi.org/10.1084/jem.20051150 Aliprantis AO, Ueki Y, Sulyanto R, Park A, Sigrist KS, Sharma SM, Ostrowski MC, Olsen BR, Glimcher LH (2008) NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism (in eng). J Clin Invest 118:3775–3789. https://doi.org/10.1172/JCI35711 Tamura T, Yanai H, Savitsky D, Taniguchi T (2008) The IRF family transcription factors in immunity and oncogenesis (in eng). Annu Rev Immunol 26:535–584. https://doi.org/10.1146/annurev.immunol.26.021607.090400 Takayanagi H, Kim S, Matsuo K, Suzuki H, Suzuki T, Sato K, Yokochi T, Oda H, Nakamura K, Ida N, Wagner EF, Taniguchi T (2002) RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta (in eng). Nature 416:744–749. https://doi.org/10.1038/416744a Ivashkiv LB, Donlin LT (2014) Regulation of type I interferon responses (in eng). Nat Rev Immunol 14:36–49. https://doi.org/10.1038/nri3581 Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL (2005) IL-1 mediates TNF-induced osteoclastogenesis (in eng). J Clin Invest 115:282–290. https://doi.org/10.1172/JCI23394 Yao Z, Xing L, Boyce BF (2009) NF-kappaB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism (in eng). J Clin Invest 119:3024–3034. https://doi.org/10.1172/JCI38716 Boyce BF, Xiu Y, Li J, Xing L, Yao Z (2015) NF-κB-mediated regulation of osteoclastogenesis (in eng). Endocrinol Metab (Seoul) 30:35–44. https://doi.org/10.3803/EnM.2015.30.1.35 Zhao B, Grimes SN, Li S, Hu X, Ivashkiv LB (2012) TNF-induced osteoclastogenesis and inflammatory bone resorption are inhibited by transcription factor RBP-J (in eng). J Exp Med 209:319–334. https://doi.org/10.1084/jem.20111566 Zhao B, Takami M, Yamada A, Wang X, Koga T, Hu X, Tamura T, Ozato K, Choi Y, Ivashkiv LB, Takayanagi H, Kamijo R (2009) Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis (in eng). Nat Med 15:1066–1071. https://doi.org/10.1038/nm.2007 Nishikawa K, Nakashima T, Hayashi M, Fukunaga T, Kato S, Kodama T, Takahashi S, Calame K, Takayanagi H (2010) Blimp1-mediated repression of negative regulators is required for osteoclast differentiation (in eng). Proc Natl Acad Sci U S A 107:3117–3122. https://doi.org/10.1073/pnas.0912779107