Fluid shear stress promotes osteoblast proliferation via the G alpha q-ERK5 signaling pathway

doi:10.1080/03008207.2016.1181063

CORC > 兰州大学 > 兰州大学 > 第二临床医学院 > 期刊论文

	Fluid shear stress promotes osteoblast proliferation via the G alpha q-ERK5 signaling pathway
	Zhang, B; Geng, B; Wang, J; Wang, CF; An, LP; Ma, JL; Jiang, J; Tan, XY; Chen, C; Ding, N
刊名	CONNECTIVE TISSUE RESEARCH
	2016
卷号	57 期号:4 页码:299-306
关键词	Cell proliferation extracellular signal-regulated kinase 5 fluid shear stress G alpha q protein osteoblast
ISSN号	0300-8207
DOI	10.1080/03008207.2016.1181063
文献子类	Article
英文摘要	Fluid shear stress (FSS) is a ubiquitous mechanical stimulus that potently promotes osteoblast proliferation. Previously, we reported that extracellular signal-regulated kinase 5 (ERK5) is essential for FSS-induced osteoblast proliferation. However, the precise mechanism by which FSS promotes osteoblast proliferation via ERK5 activation is poorly understood. The aim of this study was to determine the critical role of G alpha q in FSS-induced ERK5 phosphorylation and osteoblast proliferation, as well as the downstream targets of the G alpha q-ERK5 pathway. MC3T3-E1 cells were transfected with 50 nM G alpha q siRNA, treated with 5 mM XMD8-92 (a highly selective inhibitor of ERK5 activity), and/or exposed to FSS (12 dyn/cm(2)). Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression levels of G alpha q, P-ERK5, ERK5, Cyclin B1, and CDK1 were analyzed by Western blot. Physiological FSS exposure for 60 min remarkably promoted MC3T3-E1 cell proliferation, however, this effect was suppressed by siRNA-mediated G alpha q knockdown or inhibition of ERK5 activity by XMD8-92 treatment, suggesting that G alpha q and ERK5 might modulate FSS-increased osteoblast proliferation. Furthermore, ERK5 phosphorylation was dramatically inhibited by G alpha q siRNA. In addition, our study further revealed that FSS treatment of MC3T3-E1 cells for 60 min markedly upregulated the protein expression levels of Cyclin B1 and CDK1, and this increased expression was predominantly blocked by G alpha q siRNA or XMD8-92 treatment. We propose that FSS acts on the G alpha q-ERK5 signaling pathway to upregulate Cyclin B1 and CDK1 expression, thereby resulting in MC3T3-E1 cell proliferation. Thus, the G alpha q-ERK5 signaling pathway may provide useful information regarding the treatment of bone metabolic disease.
学科主题	Cell Biology ; Orthopedics
出版地	PHILADELPHIA
资助项目	国家自然科学基金项目 ; 国家杰出青年科学基金项目 ; 中央高校基本科研业务费专项资金 ; 甘肃省杰出青年基金计划
项目编号	National Natural Science Foundation of China [81371230, 81560361] ; National Science Foundation for Distinguished Young Scholars of Gansu Province, China [1210RJDA010] ; Fundamental Research Funds for the Central Universities [lzujbky-2014-144]
语种	英语
WOS记录号	WOS:000379227000006
资助机构	NSFC ; LZU ; GSSTD
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/179334]
专题	第二临床医学院_期刊论文
通讯作者	Xia, YY (reprint author), Lanzhou Univ, Hosp 2, Dept Orthoped, 82 Cuiyingmen, Lanzhou 730000, Gansu, Peoples R China.
推荐引用方式 GB/T 7714	Zhang, B,Geng, B,Wang, J,et al. Fluid shear stress promotes osteoblast proliferation via the G alpha q-ERK5 signaling pathway[J]. CONNECTIVE TISSUE RESEARCH,2016,57(4):299-306.
APA	Zhang, B.,Geng, B.,Wang, J.,Wang, CF.,An, LP.,...&Xia, YY .(2016).Fluid shear stress promotes osteoblast proliferation via the G alpha q-ERK5 signaling pathway.CONNECTIVE TISSUE RESEARCH,57(4),299-306.
MLA	Zhang, B,et al."Fluid shear stress promotes osteoblast proliferation via the G alpha q-ERK5 signaling pathway".CONNECTIVE TISSUE RESEARCH 57.4(2016):299-306.