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RANKL as the master regulator of osteoclast differentiation
Abstract
RANKL, the essential cue for osteoclast differentiation, is the membrane-bound factor expressed by osteoclastogenesis-supporting cells such as osteoblasts and osteocytes. In vivo evidence indicates that RANKL functions as the indispensable and irreplaceable in the program of osteoclast differentiation. The reason why RANKL plays a critical role in osteoclastogenesis is discussed from the viewpoint of the distinct signaling pathways mediated by co-stimulatory receptors and the key transcription factor NFATc1.
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“Mechanistically, M-CSF and RANKL bind to their receptors CSF1R and RANK, respectively, and stimulate downstream signaling pathways such as MAPKs and NF-κB, leading to the activation of master transcription factors including PU.1 and NFATc1, initiating osteoclastogenesis9,10.”
From Targeting Msx2 as a brake in the fusion fate of osteoclasts and an anabolic therapy in pre-clinical models of osteoporosis (2025) · cites this paper as [10]
Citations
Cites
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224
Regulation of type I interferon responses
Ivashkiv, L. B., & Donlin, L. T. (2013) · Nature reviews. Immunology · doi:10.1038/nri3581 · Cited by 3,442
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351
Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J.-I., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00369-6 · Cited by 2,701
Self-citationKulkarni, A. B., Huh, C. G., Becker, D., Geiser, A., Lyght, M., Flanders, K. C., Roberts, A. B., Sporn, M. B., Ward, J. M., & Karlsson, S. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.770 · Cited by 1,967
Yoshida, H., Hayashi, S.-I., Kunisada, T., Ogawa, M., Nishikawa, S., Okamura, H., Sudo, T., Shultz, L. D., & Nishikawa, S.-I. (1990) · Nature · doi:10.1038/345442a0 · Cited by 1,789
Evidence for osteocyte regulation of bone homeostasis through RANKL expression
Nakashima, T., Hayashi, M., Fukunaga, T., Kurata, K., Oh-hora, M., Feng, J. Q., Bonewald, L. F., Kodama, T., Wutz, A., Wagner, E. F., et al. (2011) · Nature Medicine · doi:10.1038/nm.2452 · Cited by 1,778
Self-citationGenetic regulation of osteoclast development and function
Teitelbaum, S. L., & Ross, F. P. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1122 · Cited by 1,720
RANK is essential for osteoclast and lymph node development.
Dougall, W. C., Glaccum, M., Charrier, K., Rohrbach, K., Brasel, K., De Smedt, T., Daro, E., Smith, J., Tometsko, M. E., Maliszewski, C. R., et al. (1999) · Genes & Development · doi:10.1101/gad.13.18.2412 · Cited by 1,478
The molecular understanding of osteoclast differentiation
Asagiri, M., & Takayanagi, H. (2007) · Bone · doi:10.1016/j.bone.2006.09.023 · Cited by 1,363
Self-citationMatrix-embedded cells control osteoclast formation
Xiong, J., Onal, M., Jilka, R. L., Weinstein, R. S., Manolagas, S. C., & O'Brien, C. A. (2011) · Nature Medicine · doi:10.1038/nm.2448 · Cited by 1,304
The IRF Family Transcription Factors in Immunity and Oncogenesis
Tamura, T., Yanai, H., Savitsky, D., & Taniguchi, T. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090400 · Cited by 1,259
Li, J., Sarosi, I., Yan, X.-Q., Morony, S., Capparelli, C., Tan, H.-L., McCabe, S., Elliott, R., Scully, S., Van, G., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1566 · Cited by 1,119
Wiktor-Jedrzejczak, W., Bartocci, A., Ferrante, A. W., Ahmed-Ansari, A., Sell, K. W., Pollard, J. W., & Stanley, E. R. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.12.4828 · Cited by 1,031
Autoamplification of NFATc1 expression determines its essential role in bone homeostasis
Asagiri, M., Sato, K., Usami, T., Ochi, S., Nishina, H., Yoshida, H., Morita, I., Wagner, E. F., Mak, T. W., Serfling, E., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051150 · Cited by 849
Self-citationCostimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis
Koga, T., Inui, M., Inoue, K., Kim, S., Suematsu, A., Kobayashi, E., Iwata, T., Ohnishi, H., Matozaki, T., Kodama, T., et al. (2004) · Nature · doi:10.1038/nature02444 · Cited by 832
Self-citationOsteoimmunology: evolving concepts in bone–immune interactions in health and disease
Tsukasaki, M., & Takayanagi, H. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0178-8 · Cited by 812
Self-citationTRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis.
Pettit, A. R., Ji, H., von Stechow, D., Müller, R., Goldring, S. R., Choi, Y., Benoist, C., & Gravallese, E. M. (2001) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63016-7 · Cited by 807
IL-1 mediates TNF-induced osteoclastogenesis
Shi, W., Kitaura, H., Zhou, P., Ross, F. P., & Teitelbaum, S. L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23394 · Cited by 805
RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β
Takayanagi, H., Kim, S., Matsuo, K., Suzuki, H. I., Suzuki, T., Sato, K., Yokochi, T., Oda, H., Nakamura, K., Ida, N., et al. (2002) · Nature · doi:10.1038/416744a · Cited by 719
Self-citationYasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Cited by 650
Osteoimmunology: The conceptual framework unifying the immune and skeletal systems
Okamoto, K., Nakashima, T., Shinohara, M., Negishi-Koga, T., Komatsu, N., Terashima, A., Sawa, S., Nitta, T., & Takayanagi, H. (2017) · Physiological Reviews · doi:10.1152/physrev.00036.2016 · Cited by 534
Self-citationTolar, J., Teitelbaum, S. L., & Orchard, P. J. (2004) · New England Journal of Medicine · doi:10.1056/nejmra040952 · Cited by 500
Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL
Sobacchi, C., Frattini, A., Guerrini, M. M., Abinun, M., Pangrazio, A., Susani, L., Bredius, R. G. M., Mancini, G. M. S., Cant, A. J., Bishop, N. J., et al. (2007) · Nature Genetics · doi:10.1038/ng2076 · Cited by 389
Aliprantis, A. O., Ueki, Y., Sulyanto, R. M., Park, A., Sigrist, K. S., Sharma, S. M., Ostrowski, M. C., Olsen, B. R., & Glimcher, L. H. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35711 · Cited by 350
Host defense against oral microbiota by bone-damaging T cells
Tsukasaki, M., Komatsu, N., Nagashima, K., Nitta, T., Pluemsakunthai, W., Shukunami, C., Iwakura, Y., Nakashima, T., Okamoto, K., & Takayanagi, H. (2018) · Nature Communications · doi:10.1038/s41467-018-03147-6 · Cited by 330
Self-citationTyrosine Kinases Btk and Tec Regulate Osteoclast Differentiation by Linking RANK and ITAM Signals
Shinohara, M., Koga, T., Okamoto, K., Sakaguchi, S., Arai, K., Yasuda, H., Takai, T., Kodama, T., Morio, T., Geha, R. S., et al. (2008) · Cell · doi:10.1016/j.cell.2007.12.037 · Cited by 327
Self-citationNF-κB-Mediated Regulation of Osteoclastogenesis
Boyce, B. F., Xiu, Y., Li, J., Xing, L., & Yao, Z. (2015) · Endocrinology and Metabolism · doi:10.3803/enm.2015.30.1.35 · Cited by 320
Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis
Zhao, B., Takami, M., Yamada, A., Wang, X., Koga, T., Hu, X., Tamura, T., Ozato, K., Choi, Y., Ivashkiv, L. B., et al. (2009) · Nature Medicine · doi:10.1038/nm.2007 · Cited by 316
Self-citationHuman Osteoclast-Poor Osteopetrosis with Hypogammaglobulinemia due to TNFRSF11A (RANK) Mutations
Guerrini, M. M., Sobacchi, C., Cassani, B., Abinun, M., Kilic, S. S., Pangrazio, A., Moratto, D., Mazzolari, E., Clayton-Smith, J., Orchard, P., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.06.015 · Cited by 309
Danks, L., Komatsu, N., Guerrini, M. M., Sawa, S., Armaka, M., Kollias, G. A., Nakashima, T., & Takayanagi, H. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2014-207137 · Cited by 245
Self-citationZhao, B., Grimes, S. N., Li, S., Hu, X., & Ivashkiv, L. B. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20111566 · Cited by 182
Blimp1-mediated repression of negative regulators is required for osteoclast differentiation
Nishikawa, K., Nakashima, T., Hayashi, M., Fukunaga, T., Kato, S., Kodama, T., Takahashi, S., Calame, K. L., & Takayanagi, H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912779107 · Cited by 171
Self-citationRANK‐Independent Osteoclast Formation and Bone Erosion in Inflammatory Arthritis
O’Brien, W. M., Fissel, B. M., MAEDA, Y. Y., Yan, J., Ge, X., Gravallese, E. M., Aliprantis, A. O., & Charles, J. F. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39837 · Cited by 152
NF-κB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism
Yao, Z., Xing, L., & Boyce, B. F. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38716 · Cited by 151
Immune complexes regulate bone metabolism through FcRγ signalling
Negishi‐Koga, T., Gober, H.-J., Sumiya, E., Komatsu, N., Okamoto, K., Sawa, S., Suematsu, A., Suda, T., Sato, K., Takai, T., et al. (2015) · Nature Communications · doi:10.1038/ncomms7637 · Cited by 141
Self-citationLocal Production of Osteoprotegerin by Osteoblasts Suppresses Bone Resorption
Cawley, K. M., Bustamante-Gomez, N. C., Guha, A. G., MacLeod, R. S., Xiong, J., Gubrij, I., Liu, Y., Mulkey, R., Palmieri, M., Thostenson, J. D., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108052 · Cited by 114
OPG Production Matters Where It Happened
Tsukasaki, M., Asano, T., Muro, R., Huynh, N. C., Komatsu, N., Okamoto, K., Nakano, K., Okamura, T., Nitta, T., & Takayanagi, H. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108124 · Cited by 107
Self-citationNakamichi, Y., Mizoguchi, T., Arai, A., Kobayashi, Y., Sato, M., Penninger, J. M., Yasuda, H., Kato, S., DeLuca, H. F., Suda, T., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207361109 · Cited by 74
Vargas, S. J., Naprta, A., Glaccum, M. B., Lee, S. K., Kalinowski, J., & Lorenzo, J. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650111117 · Cited by 60
LOX Fails to Substitute for RANKL in Osteoclastogenesis
Tsukasaki, M., Hamada, K., Okamoto, K., Nagashima, K., Terashima, A., Komatsu, N., Win, S. J., Okamura, T., Nitta, T., Yasuda, H., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2990 · Cited by 54
Self-citationRANKL-Independent Osteoclastogenesis: A Long-Standing Controversy
Tanaka, S. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3092 · Cited by 39
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The RANK/RANKL/OPG system and tumor bone metastasis: Potential mechanisms and therapeutic strategies
Zhang, Y., Liang, J., Liu, P., Wang, Q., Liu, L., & Zhao, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1063815 · Cited by 111
Xue, C., Luo, H., Wang, L., Deng, Q., Kui, W., Da, W., Chen, L., Liu, S., Xue, Y., Yang, J., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1234563 · Cited by 70
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Zhao, Y., Ning, J., Teng, H., Deng, Y., Sheldon, M., Shi, L., Martinez, C., Zhang, J., Tian, A., Sun, Y., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46602-3 · Cited by 69
Faqeer, A., Wang, M., Alam, G., Padhiar, A. A., Zheng, D., Luo, Z., Zhao, I. S., Zhou, G., van den Beucken, J. J. J. P., Wang, H., et al. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122367 · Cited by 62
Metadata
- Authors
- Takayanagi, H.
- Affiliations
- The University of Tokyo (JP)
- Corresponding author
- Takayanagi, Hiroshi
- ORCID
- Takayanagi, Hiroshi
- Venue
- Journal of Bone and Mineral Metabolism
- Published
- 2021-01
- Volume
- 39
- Issue
- 1
- Pages
- 13-18
- ISSN
- 0914-8779 (ISSN-L)
- 1435-5604
- OpenAlex
- W3116940347
- Cited by
- 175
- References
- 43
- Citations by year
- 2026: 29 · 2025: 38 · 2024: 35 · 2023: 38 · 2022: 25 · 2021: 9
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Bone and Mineral Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (20F20730)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Keywords
- RANKL, osteoclastogenesis, RANK receptor, costimulatory receptors, NFATc1, transcription factor signaling, osteoblasts, osteocytes, bone remodeling
- MeSH terms
- Animals, Humans, Osteoblasts, Osteoclasts, Osteogenesis, Signal Transduction, NFATC Transcription Factors, RANK Ligand
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