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Early estrogen-induced gene 1 facilitates osteoclast formation through the inhibition of interferon regulatory factor 8 expression
- Title
- Early estrogen-induced gene 1 facilitates osteoclast formation through the inhibition of interferon regulatory factor 8 expression
- Authors
- Jeong, Eutteum; Kim, Jihee; Go, Miyeon; Lee, Soo Young
- Ewha Authors
- 이수영
- SCOPUS Author ID
- 이수영
- Issue Date
- 2020
- Journal Title
- FASEB JOURNAL
- ISSN
- 0892-6638
1530-6860
- Citation
- FASEB JOURNAL vol. 34, no. 9, pp. 12894 - 12906
- Keywords
- bone; bone loss; osteoclast formation; osteoclastogenesis; osteoclasts
- Publisher
- WILEY
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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.
- DOI
- 10.1096/fj.202001197R
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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