Foxc2 regulates osteogenesis and angiogenesis of bone marrow mesenchymal stem cells

BMC Musculoskeletal Disorders

Research Article

Hongwei Gao¹  Dapeng Duan²  Kunzheng Wang²  Lihong Fan²  Chunsheng Wang²  Wulin You² 

[1] Department of Orthopedics, The Ninth Hospital of Xi’an Jiaotong University, 710000, Xi’an, Shaanxi Province, China;Department of Orthopedics, The Second Affilliated Hospital of Xi’an Jiaotong University, Xiwu Road, 710004, Xi’an, Shaanxi Province, China;

关键词: Bone marrow mesenchymal stem cells;    Foxc2;    Osteogenesis;    Angiogenesis;    Differentiation;   

DOI  :  10.1186/1471-2474-14-199

 received in 2013-04-05, accepted in 2013-06-28,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe Forkhead/Fox transcription factor Foxc2 is a critical regulator of osteogenesis and angiogenesis of cells. Bone marrow mesenchymal stem cells (BMSCs) have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes and fibroblasts. The present study investigates the role of Foxc2 overexpression in osteogenesis and angiogenesis of BMSCs in vitro.MethodsBMSCs were isolated from SD rat femurs and tibias, and characterized by cell surface antigen identification and osteoblasts and adipocytes differentiation. The cells were transfected with lentiviral Foxc2 (Lv-Foxc2) or green fluorescent protein (Lv-GFP). Seventy hours later, Foxc2 expression was observed using real time-PCR and Western blot. The transfected cells were stained with Alizarin red S or alkaline phosphatase (ALP) after osteogenic induction. Meanwhile, the expression levels of osteocalcin (OCN), Runt-related transcription factor 2 (Runx2), vascular endothelial growth factor (VEGF) and platelet-derived growth factor-β (PDGF-β) were measured by real time-PCR, Western blot and immunostaining.ResultsResults of cell characterization showed that the cells were positive to CD44 (99.56%) and negative to CD34 (0.44%), and could differentiate into osteoblasts and adipocytes. Foxc2 overexpression not only increased the numbers of mineralized nodes and ALP activity, but also enhanced the expressions of Runx2, OCN, VEGF and PDGF-β in transfected BMSCs after osteogenic induction. The effects of Foxc2 on osteogenesis and angiogenesis were significantly different between Lv-Foxc2 transfected BMSCs and Lv-GFP transfected BMSCs (P<0.05). In addition, the MAPK-specific inhibitors, PD98059 and LY294002, blocked the Foxc2-induced regulation of BMSC differentiation.ConclusionsFoxc2 gene is successfully transfected into BMSCs with stable and high expression. The overexpression of Foxc2 acts on BMSCs to stimulate osteogenesis and angiogenesis. The effect of Foxc2 on angiogenesis of the cells is mediated via activating PI3K and ERK.

【 授权许可】

Unknown   
© You et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.