title: EGCG ameliorates the hypoxia-induced apoptosis and osteogenic differentiation reduction of mesenchymal stem cells via upregulating miR-210.
abstract: The healing process of fractured bone is affected by the multiple factors regulating the growth and differentiation of osteoblasts and bone mesenchymal stem cells (MSCs), however, such markers and molecular events need to be orchestrated in details. This study investigated the effect of polyphenol(-)-epigallocatechin-3-gallate (EGCG) on the hypoxia-induced apoptosis and osteogenic differentiation of human bone marrow-derived MSCs, examined the miR-210 induction by EGCG, explored the target inhibition of the expression of receptor tyrosine kinase ligand ephrin-A3 (EFNA3) by miR-210, and then determined the association of the miR-210 promotion with the hypoxia-induced apoptosis and osteogenic differentiation. Results demonstrated that EGCG treatment significantly inhibited the hypoxia-induced apoptosis in MSCs and promoted the level of alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2), propeptide of type I procollagen I (PINP) and runt-related transcription factor 2 (RUNX2) in MSCs under either normoxia or hypoxia. Moreover, the EGCG treatment upregulated the miR-210 expression, in an association with EFNA3 downregulation; and the miR-210 upregulation significantly downregulated the expression of EFNA3 via the specific binding to the 3' UTR of EFNA3. In addition, the manipulated miR-210 upregulation exerted amelioration on the hypoxia-induced apoptosis and on the hypoxia-reduced expression of ALP, BMP-2, PINP and RUNX2 in MSCs. In summary, our study indicated the protective role of EGCG in response to hypoxia and promontory role to osteogenic differentiation in MSCs via upregulating miR-210 and downregulating the expression of miR-210-targeted EFNA3. Our study implies the protective role of EGCG in the hypoxia-induced impairment in MSCs.
authors.affiliation: Department of Spine Surgery, The 2nd Shenzhen People's Hospital, No. 3002, Sungang Road, Futian District, Shenzhen, 510000, China.
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Spine Surgery, The 2nd Shenzhen People's Hospital, No. 3002, Sungang Road, Futian District, Shenzhen, 510000, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Spine Surgery, The 2nd Shenzhen People's Hospital, No. 3002, Sungang Road, Futian District, Shenzhen, 510000, China.
authors.forename: Tenghui
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Department of Spine Surgery, The 2nd Shenzhen People's Hospital, No. 3002, Sungang Road, Futian District, Shenzhen, 510000, China.
authors.forename: Weizhuang
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Spine Surgery, The 2nd Shenzhen People's Hospital, No. 3002, Sungang Road, Futian District, Shenzhen, 510000, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Spine Surgery, The 2nd Shenzhen People's Hospital, No. 3002, Sungang Road, Futian District, Shenzhen, 510000, China. jianxin6265@sina.com.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Yang
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015687:Cell Hypoxia; D024042:Collagen Type I / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D036384:Ephrin-A3 / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics*; D010012:Osteogenesis / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D036384:Ephrin-A3; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; C493709:RUNX2 protein, human; D002392:Catechin; C045651:epigallocatechin gallate; D000469:Alkaline Phosphatase
keywords: Apoptosis; EFNA3; EGCG; Mesenchymal stem cells; Osteogenic differentiation; miR-210