title: 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.
abstract: 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 17β 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 (ERα/β) by fulvestrant and ERα 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 ERα/β pathway, and sensitized osteocytes to mechanical loading.
authors.affiliation: Imaging & Characterization lab, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
authors.forename: Jian
authors.initials: J
authors.lastname: Ren
authors.forename: Xu-Hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Guang-Chao
authors.initials: GC
authors.lastname: Wang
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Wu
mesh_terms: D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D036681:Fluorescence Recovery After Photobleaching; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D010011:Osteocytes / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D018031:Connexin 43; D004958:Estradiol