title: Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system.
abstract: Mechanical stimuli and neovascularization are closely coupled to osteogenic differentiation and new bone formation. The purpose of present study was to detect the effect of cyclic mechanical strain on a co-culture system of bone marrow stromal cells (BMSCs) and vascular endothelial cells (VECs) and to clarify the related mechanisms. Primary BMSCs and VECs were isolated from Sprague-Dawley rats and co-cultured at various ratios (1:0, 1:2, 1:4, 4:1, 2:1, 1:1, and 0:1). To determine optimized loading conditions, the cells were then subjected to various cyclic tensile strains (0%, 3%, 6% and 9%) using a Flexcell 5000 mechanical loading system. A protocol of 6% strain on the co-cultured cells at a 1:1 ratio was selected as the optimized culture conditions based on the best osteogenic effects, which included increased ALP activity, matrix mineralization and the expressions of VEGF, Runx-2 and Col-1. The VEGF-R inhibitor tivozanib was used to analyze the paracrine role of VEGF, and the osteogenesis-promoting effects of 6% tensile strain were abrogated in the co-cultured cells treated with tivozanib. These results demonstrate that cyclic tensile strain promotes osteogenic differentiation in BMSC/VEC co-culture systems, possibly via a VEC-mediated paracrine effect of VEGF on BMSCs.
authors: Department of Orthodontics, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China.
authors: Yunan
authors: Y
authors: Jiang
authors: Department of Orthodontics, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China.
authors: Yu
authors: Y
authors: Wang
authors: Department of Orthodontics, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China. Electronic address: tangg@graduate.hku.hk.
authors: Guohua
authors: G
authors: Tang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D013314:Stress, Mechanical; D013718:Tensile Strength; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit; D010671:Phenylurea Compounds; D011804:Quinolines; C493717:Runx2 protein, rat; D042461:Vascular Endothelial Growth Factor A; C553176:tivozanib; C010078:alizarin; D040262:Receptors, Vascular Endothelial Growth Factor; D000469:Alkaline Phosphatase
keywords: BMSC; Co-culture; Cyclic tensile strain; Osteogenic differentiation; VEGF; Vascular endothelial cell