[No authors listed]
The occurrence of pelvic organ prolapse (POP) is closely associated with alterations in the extracellular matrix proteins of the supporting ligament. Bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into a variety of cell types, including osteoblasts, chondroblasts and adipocytes. Therefore, BMSCs have the potential to improve the clinical outcomes of POP. TenascinâC is a large glycoprotein that is present in the ECM and is involved in morphogenetic movements, and tissue patterning and repair. The aim of the present study was to investigate the effect of mechanical stretching on tenascinâC expression during the differentiation of BMSCs induced by pelvic ligament fibroblasts. BMSCs were isolated from 7âdayâold Sprague Dawley rats. Fibroblasts were obtained from rat pelvic ligaments and, at the fourth passage, were subjected to 10% deformation with 1 Hz, periodic oneâway mechanical stretch stimulation, followed by coâculture with BMSCs. The coâculture with stretched fibroblasts increased tenascinâC and transforming growth factor (TGF)âβ expression levels, compared with groups without mechanical stimulation. Neutralizing antiâTGFâβ1 antibodies, and inhibitors of TGFâβ receptor, mitogenâactivated protein kinase (MAPK) kinase and MAPK, decreased tenascinâC expression levels induced by TGFâβ and mechanical stretching. The results of the present study suggested that the regulation of tenascinâC expression levels in BMSCs coâcultured with mechanically stretched pelvic ligament fibroblasts is mediated via the soluble growth factor TGFâβ and the MAPK signaling pathway. In addition, these results indicated that in an indirect coâculture system, pelvic ligament fibroblasts with mechanical stretch stimulation may promote the synthesis of tenascinâC and BMSC differentiation into pelvic ligament fibroblasts.
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