Cited by 60Bone Metabolism and DiseasesOsteomyelitis and Bone Disorders ResearchBone and Dental Protein Studies

Role and Regulation of Transcription Factors in Osteoclastogenesis

Open access
Jiang, Tao, Xia, Tianshuang, Qiao, Fangliang, Wang, Nani, Jiang, Yiping, Xin, Hailiang·2023·International Journal of Molecular Sciences

Abstract

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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Crossref · 10.3390/ijms242216175

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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)
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
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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