Interleukin-10 inhibits RANKL-mediated expression of NFATc1 in part via suppression of c-Fos and c-Jun in RAW264.7 cells and mouse bone marrow cells
Abstract
Interleukin-10 (IL-10), an anti-inflammatory cytokine, has been shown to inhibit osteoclast formation and bone resorption in rat and mouse systems. However, the precise intracellular mechanism(s) of this action remains unclear. The aim of this study was to clarify the role of IL-10 in the regulation of critical transcription factors involved in osteoclastogenesis. A RAW264.7 macrophage cell line, which constitutively expressed IL-10 receptor, was differentiated to osteoclasts with stimulation of receptor activator of nuclear factor kappaB ligand (RANKL). IL-10 inhibited the RANKL-induced osteoclastogenesis. IL-10 potently reduced the RANKL-induced expression of NFATc1, c-Jun and c-Fos, which are known to be essential for osteoclastogenesis, in time- and dose-dependent manners. The IL-10-induced inhibition of these transcription factors was observed in the system of mouse bone marrow precursors. Besides these transcription factors, IL-10 also decreased the RANKL-induced expression of NF-kappaB p50 and phosphorylation of JNK. To determine which signaling was critical for the IL-10 effect, we examined the effect of overexpression of NFATc1, c-Fos, and c-Jun on the IL-10-induced inhibition of osteoclastogenesis. As expected, overexpression of NFATc1 abrogated the IL-10-induced inhibition of osteoclastogenesis. Interestingly, overexpression of either c-Fos or c-Jun partially rescued the reduction of RANKL-induced expression of NFATc1 and osteoclastogenesis by IL-10. These data sug…
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IL-10 inhibits osteoclastogenesis by downregulating RANKL-induced expression of c-Fos and its downstream target NFATc1.
“Using a RAW267.4 macrophage cell line and murine bone marrow cells, Mohamed and associates reported that IL-10 inhibited osteoclastogenesis by downregulating RANKL-induced expression of c-Fos and its downstream target, NFATc1 [43].”
From Osteoclasts and Microgravity (2020) · cites this paper as [43]
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“RANKL, a member of the tumor necrosis factor (TNF) cytokine superfamily, is critical for the differentiation and fusion of precursors into mature osteoclasts [5–9].”
BackgroundThe jun proto-oncogene is positively autoregulated by its product, Jun/AP-1
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Regulation of TNF-Induced Osteoclast Differentiation
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“This loss was associated with an upregulation in osteoclastogenesis-related signaling molecules ERK, p38, PLCγ2, and NFATc1 and osteoclast-specific markers TRAP and cathepsin K.”
BackgroundInfluential
- Authors
- Mohamed, S. G.-K., Sugiyama, E., Shinoda, K., Taki, H., Hounoki, H., Abdel-Aziz, H. O., Maruyama, M., Kobayashi, M., Ogawa, H., & Miyahara, T.
- Affiliations
- University of Toyama (JP)
- Corresponding author
- Sugiyama, Eiji
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 41
- Issue
- 4
- Pages
- 592-602
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- OpenAlex
- W2007076579
- Cited by
- 120
- References
- 5
- Citations by year
- 2026: 10 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 11 · 2019: 4 · 2018: 9 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 16 · 2013: 9 · 2012: 5
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bone (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- 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 › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-10, RANKL, osteoclastogenesis, NFATc1, c-fos, c-Jun, transcription factors, NF-κB p50, JNK phosphorylation, bone resorption, RAW 264.7 macrophages, bone marrow precursors, anti-inflammatory cytokines
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Cell Line, Humans, Osteoclasts, Phosphorylation, RNA, Messenger, Interleukin-10, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-fos, Transcription Factor AP-1, NFATC Transcription Factors, Mice, NF-kappa B p50 Subunit, RANK Ligand, Receptors, Interleukin-10
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