Effects of compressive force on the differentiation of pluripotent mesenchymal cells

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• 作者：Momoko Yanagisawa ; Naoto Suzuki ; Narihiro Mitsui ; Yuki Koyama ; Kichibee Otsuka ; Noriyoshi Shimizu
• 关键词：Mechanical stress ; C2C12 cells ; Osteogenesis ; Runx2 ; p38 MAPK
• 刊名：Life Sciences
• 出版年：2007
• 出版时间：12 July 2007
• 年：2007
• 卷：81
• 期：5
• 页码：405-412
• 全文大小：792 K

文摘

The purpose of this study was to determine the effect of mechanical stress on the differentiation of the pluripotent mesenchymal cell line C2C12. C2C12 cells were cultured continuously under compressive force (0.25–2.0 g/cm²). After mechanical stress loading, the levels of expression of mRNAs and proteins for phenotype-specific markers of osteoblasts (Runx2, Msx2, Dlx5, Osterix, AJ18), chondroblasts (Sox5, Sox9), myoblasts (MyoD), and adipocytes (PPARγ) were measured by real-time polymerase chain reaction analysis and Western blot analysis, respectively. The expression of activated p38 mitogen-activated protein kinase (p38 MAPK) was measured by Western blotting and/or ELISA. Loading 0.5 g/cm² of compressive force significantly increased the expression levels of Runx2, Msx2, Dlx5, Osterix, Sox5, and Sox9. In contrast, the expression levels of AJ18, MyoD, and PPARγ were decreased by exposure to 0.5 g/cm² of compressive force. Loading 0.5 g/cm² of compressive force also induced the phosphorylation of p38 MAPK. SB203580, which is a specific inhibitor of p38 MAPK, inhibited the compressive force-induced phosphorylation of p38 MAPK and partially blocked compressive force-induced Runx2 mRNA expression. These results demonstrate that compressive force stimulation directs the differentiation pathway of C2C12 cells into the osteoblast and chondroblast lineage via activated phosphorylation of p38 MAPK.