The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
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.
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Regulation of type I interferon responses
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OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
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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
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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.
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Cited by
Sorted by citations
The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases
Yao, Y., Cai, X. T., Ren, F., Ye, Y., Wang, F., Zheng, C., Qian, Y., & Zhang, M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.664871 · Cited by 235
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
Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis
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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