Early estrogen-induced gene 1 facilitates osteoclast formation through the inhibition of interferon regulatory factor 8 expression
- 주제(키워드) bone , bone loss , osteoclast formation , osteoclastogenesis , osteoclasts
- 주제(기타) Biochemistry & Molecular Biology
- 주제(기타) Biology
- 주제(기타) Cell Biology
- 설명문(일반) [Jeong, Eutteum; Kim, Jihee; Go, Miyeon; Lee, Soo Young] Ewha Womans Univ, Dept Life Sci, C-419,Sci Complex Bldg,52 Ewhayeodae Gil, Seoul 03760, South Korea; [Jeong, Eutteum; Kim, Jihee; Lee, Soo Young] Ewha Womans Univ, Res Ctr Cellular Homeostasis, C-419,Sci Complex Bldg,52 Ewhayeodae Gil, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- OA유형 hybrid
- 발행기관 WILEY
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000174500
- 본문언어 영어
- Published As http://dx.doi.org/10.1096/fj.202001197R
- PubMed https://pubmed.ncbi.nlm.nih.gov/32741026
초록/요약
Osteoclast-mediated inflammatory bone resorption is a major cause of many inflammatory bone disorders, including rheumatoid arthritis and periodontitis. However, the mechanisms regulating osteoclast differentiation in inflammatory settings are not well understood. We demonstrate here that early estrogen-induced gene 1 (EEIG1)-deficient mice are protected from inflammatory bone loss as determined with the use of models of lipopolysaccharide (LPS)-induced bone destruction.EEIG1-deficient macrophages markedly decreased RANKL- and TNF alpha-mediated osteoclastogenesis due to the downregulation of the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), which is an essential transcription factor for osteoclast formation. In contrast, expression of interferon regulatory factor 8 (IRF8), a transcriptional repressor that blocks osteoclast differentiation, is elevated inEEIG1-deficient macrophages relative to wild-type cells. We found that reduced expression of B lymphocyte-induced maturation protein-1 (Blimp1) by siRNA downregulated RANKL-induced EEIG1 levels, whereas overexpression of Blimp1 potentiated EEIG1 levels. Mechanistic studies revealed that EEIG1 forms a complex with Blimp1 to negatively regulate the expression of the anti-osteoclastogenic gene,Irf8. We elucidated a novel mechanism by which EEIG1 restricts IRF8 expression and function, thereby enhancing the osteoclast formation by contributing to Blimp1-mediated IRF8 regulation. Together, these findings identify EEIG1 as a key regulator of osteoclastogenesis and a possible therapeutic target for pathological bone destruction.
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