title: The Distinct Effects of Estrogen and Hydrostatic Pressure on Mesenchymal Stem Cells Differentiation: Involvement of Estrogen Receptor Signaling.
abstract: This study aimed to investigate the differential and synergistic effects of mechanical stimulation and estrogen on the proliferation and osteogenic or chondrogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs) and the roles of estrogen receptor (ER) in them. BMSCs were isolated and cultured using the whole bone marrow adherence method, and flow cytometry was used to identify the surface marker molecules of BMSCs. Cells were pre-treated with 1 nM 17β-estradiol or 1 nM of the estrogen receptor antagonist tamoxifen. Then, the cells were stimulated with hydrostatic pressure. Assessment included flow cytometry analysis of the cell cycle; immunofluorescent staining for F-actin; protein quantification for MAPK protein; and mRNA analysis for Col I, OCN, OPN and BSP after osteogenic induction and Sox-9, Aggrecan and Col-II after chondrogenic induction. Hydrostatic pressure (90 kPa/1 h) and 1 nM 17β-estradiol enhanced the cellular proliferation ability and the cytoskeleton activity but without synergistic biological effects. Estrogen activated ERKs and JNKs simultaneously and promoted the osteogenic differentiation, whereas the pressure just caused JNK-1/2 activation and promoted the chondrogenic differentiation of BMSCs. Estrogen had antagonism effect on chondrogenic promotion of hydrostatic pressure. Mechanobiological effects of hydrostatic pressure are closely associated with ERα activity. MAPK molecules and F-actin were likely to be important mediator molecules in the ER-mediated mechanotransduction of BMSCs.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, China.|Department of Physiology, School of Basic Medicine, Fourth Military Medical University, No. 169 West Changle Road, Xi'an, 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The 105th Hospital of PLA, No.424 West ChangJiang Road, Hefei, 230031, China.
authors.forename: Fei-Zhou
authors.initials: FZ
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Military Stomatology, Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, China.
authors.forename: Yin-Hua
authors.initials: YH
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, China.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Basic Medicine, Fourth Military Medical University, No. 169 West Changle Road, Xi'an, 710032, China. hengma@fmmu.edu.cn.|Department of Pathophysiology, School of Basic Medicine, Fourth Military Medical University, No. 169 West Changle Road, Xi'an, 710032, China. hengma@fmmu.edu.cn.
authors.forename: Heng
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Military Stomatology, Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, China. zhangmin@fmmu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism*; D005260:Female; D006874:Hydrostatic Pressure; D020935:MAP Kinase Signaling System / Q000187:drug effects; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D047628:Estrogen Receptor alpha; D013629:Tamoxifen; D004958:Estradiol
keywords: Bone marrow mesenchymal stem cells (BMSCs); Differentiation; Estrogen; Estrogen receptor (ER); Hydrostatic pressure; Mitogen-activated protein kinase (MAPK)