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Updated: Jan 8, 2026
11:52
Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
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Interaction Between Activating Transcription Factor 4 and Interleukin 6 Dictates Osteoclast Differentiation and
Shasha Tu1, Sijun Liu1, Mengmeng Duan2
1Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
Summary
Activating transcription factor 4 (Atf4) directly binds the interleukin 6 (IL6) promoter, driving osteoclast formation. This Atf4-IL6 pathway impacts bone homeostasis and offers insights into osteoporosis treatments.
Area of Science:
- Molecular Biology
- Cell Biology
- Bone Biology
Background:
- Osteoclast function is crucial for bone homeostasis, repair, and remodeling.
- Osteoclastogenesis is regulated by transcription factors and cytokines, but the interplay between Atf4 and IL6 remains unclear.
Purpose of the Study:
- To investigate the interaction between Atf4 and IL6 in osteoclast differentiation and activity.
- To elucidate the molecular mechanisms underlying Atf4-mediated osteoclastogenesis.
Main Methods:
- Lentiviral overexpression and siRNA transfection were used to manipulate Atf4 levels.
- Chromatin immunoprecipitation (ChIP) assay was employed to assess Atf4 binding to the IL6 promoter.
- Expression of osteoclast markers and activation of signaling pathways were analyzed.
Main Results:
- Atf4 overexpression upregulated key osteoclast markers (Nfatc1, c-Fos, Dcst1, Mmp2/9, cathepsin K).
- Atf4 directly bound to the IL6 promoter, indicating transcriptional regulation of IL6 by Atf4.
- The Atf4-IL6 axis activated Jak1/Stat3 signaling, promoting the formation of large, multinucleated osteoclasts.
Conclusions:
- A novel Atf4-IL6 signaling axis significantly contributes to osteoclast differentiation, independent of canonical MCSF and RANKL pathways.
- This finding highlights the complex regulatory mechanisms of osteoclastogenesis.
- Understanding this pathway provides insights into osteoporotic diseases and potential therapeutic strategies.
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