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https://hdl.handle.net/10316/106699
Título: | Estrogens decrease osteoclast number by attenuating mitochondria oxidative phosphorylation and ATP production in early osteoclast precursors | Autor: | Kim, Ha-Neui Ponte, Filipa Nookaew, Intawat Ucer Ozgurel, Serra Carvalho, Adriana Marques Iyer, Srividhya Warren, Aaron Aykin-Burns, Nukhet Krager, Kimberly Sardão, Vilma A. Han, Li de Cabo, Rafael Zhao, Haibo Jilka, Robert L. Manolagas, Stavros C. Almeida, Maria |
Data: | 20-Jul-2020 | Editora: | Springer Nature | Projeto: | Department of Veterans Affairs (I01 BX001405) National Institutes of Health (P01 AG013918, R01 AR056679, P20 GM125503, P20 GM109005) UAMS Tobacco Funds and Translational Research Institute (1UL1RR029884) Intramural Research Program of the National Institute on Aging of the National Institutes of Health |
Título da revista, periódico, livro ou evento: | Scientific Reports | Volume: | 10 | Número: | 1 | Resumo: | Loss of estrogens at menopause is a major cause of osteoporosis and increased fracture risk. Estrogens protect against bone loss by decreasing osteoclast number through direct actions on cells of the myeloid lineage. Here, we investigated the molecular mechanism of this effect. We report that 17β-estradiol (E2) decreased osteoclast number by promoting the apoptosis of early osteoclast progenitors, but not mature osteoclasts. This effect was abrogated in cells lacking Bak/Bax-two pro-apoptotic members of the Bcl-2 family of proteins required for mitochondrial apoptotic death. FasL has been previously implicated in the pro-apoptotic actions of E2. However, we show herein that FasL-deficient mice lose bone mass following ovariectomy indistinguishably from FasL-intact controls, indicating that FasL is not a major contributor to the anti-osteoclastogenic actions of estrogens. Instead, using microarray analysis we have elucidated that ERα-mediated estrogen signaling in osteoclast progenitors decreases "oxidative phosphorylation" and the expression of mitochondria complex I genes. Additionally, E2 decreased the activity of complex I and oxygen consumption rate. Similar to E2, the complex I inhibitor Rotenone decreased osteoclastogenesis by promoting osteoclast progenitor apoptosis via Bak/Bax. These findings demonstrate that estrogens decrease osteoclast number by attenuating respiration, and thereby, promoting mitochondrial apoptotic death of early osteoclast progenitors. | URI: | https://hdl.handle.net/10316/106699 | ISSN: | 2045-2322 | DOI: | 10.1038/s41598-020-68890-7 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
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Estrogens-decrease-osteoclast-number-by-attenuating-mitochondria-oxidative-phosphorylation-and-ATP-production-in-early-osteoclast-precursorsScientific-Reports.pdf | 2.13 MB | Adobe PDF | Ver/Abrir |
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