期刊
BONE
卷 53, 期 2, 页码 587-596出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2012.12.004
关键词
Osteocyte; Estrogen receptors; Connexin 43; Mechanosensitivity
资金
- Nature Science Foundation of Shanghai, China [11ZR1440700]
- Scientific research Funds for distinguished Young Scholar of Shanghai colleges and universities [1504144003, 1504144502]
Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication (GJIC) remain obscure. We found that 17 beta estradiol (E2) up-regulated Cx43, and enhanced GJIC in osteocyte-like MLO-Y4 cells in fluorescence recovery after photobleaching (FRAP) assay. Combination of E2 pre-treatment and oscillating fluid flow (OFF) further enhanced Cx43 expression and mitogen-activated protein kinase (MAPK) phosphorylation, comparing to E2 or OFF treatment alone. Both blocking of classical estrogen receptors (ER alpha/beta) by fulvestrant and ER alpha knockdown by small interfering RNA inhibited E2-mediated Cx43 increase, while a GPR30-specific agonist G-1 failed to promote Cx43 expression. Our results suggest that the presence of E2 enhanced Cx43-based GJIC mainly via ER alpha/beta pathway, and sensitized osteocytes to mechanical loading. (c) 2012 Elsevier Inc. All rights reserved.
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