Role and Regulation of Transcription Factors in Osteoclastogenesis
Open accessAbstract
Bones serve mechanical and defensive functions, as well as regulating the balance of calcium ions and housing bone marrow.. The qualities of bones do not remain constant. Instead, they fluctuate throughout life, with functions increasing in some situations while deteriorating in others. The synchronization of osteoblast-mediated bone formation and osteoclast-mediated bone resorption is critical for maintaining bone mass and microstructure integrity in a steady state. This equilibrium, however, can be disrupted by a variety of bone pathologies. Excessive osteoclast differentiation can result in osteoporosis, Paget’s disease, osteolytic bone metastases, and rheumatoid arthritis, all of which can adversely affect people’s health. Osteoclast differentiation is regulated by transcription factors NFATc1, MITF, C/EBPα, PU.1, NF-κB, and c-Fos. The transcriptional activity of osteoclasts is largely influenced by developmental and environmental signals with the involvement of co-factors, RNAs, epigenetics, systemic factors, and the microenvironment. In this paper, we review these themes in regard to transcriptional regulation in osteoclastogenesis.
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M-CSF and RANKL activate PU.1 and NFATc1 via MAPKs and NF-κB, initiating osteoclastogenesis.
“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 [9]
Sections 4.1 and 5.8 describe M-CSF binding CSF-1R and RANKL binding RANK, with downstream MAPK and NF-κB signaling. Section 5.1 links NF-κB and p38 signaling to NFATc1 induction. But sections 3 and 5.4 do not establish that those pathways activate PU.1; they describe early PU.1 expression and its role in promoting NFATc1 expression. Page numbers were not provided in our copy. (LLM, conf=0.87)
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- Authors
- Jiang, T., Xia, T., Qiao, F., Wang, N., Jiang, Y., & Xin, H.
- Affiliations
- Fujian University of Traditional Chinese Medicine (CN)
- Second Military Medical University (CN)
- Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China
- Corresponding author
- Jiang, Yiping
- Xin, Hailiang
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2023-11-10
- Volume
- 24
- Issue
- 22
- Pages
- 16175
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC10671247
- OpenAlex
- W4388635411
- Cited by
- 60
- References
- 253
- Citations by year
- 2026: 18 · 2025: 30 · 2024: 12
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82004015, 82174079, 21S21902600)
- Project of Science and Technology Commission of Shanghai Municipality (82004015, 82174079, 21S21902600)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- osteoclastogenesis, transcription factors, transcriptional regulation, bone resorption, bone formation, osteoporosis, Paget's disease, bone metastasis, rheumatoid arthritis, NFATc1, MITF, C/EBPα, PU.1, NF-κB, c-fos, epigenetics, bone microenvironment
- MeSH terms
- Bone Resorption, Cell Differentiation, Humans, Osteoclasts, Osteogenesis, Signal Transduction, NF-kappa B, Proto-Oncogene Proteins c-fos, NFATC Transcription Factors, RANK Ligand
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