Estrogens decrease osteoclast number by attenuating mitochondria oxidative phosphorylation and ATP production in early osteoclast precursors.

ABSTRACT: 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 con

SUBMITTER: Kim HN 

PROVIDER: S-EPMC7371870 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature