Analysis of molecular mechanism of muscle heterotopic ossification by forming a network with CCN family proteins

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The protein production of CCN2 (also known as Connective tissue growth factor) was increased in mouse myoblastic cell line C2C12 by treatment with tumor necrosis factor-a, which is produced upon inflammation. CCN2 promoted cell proliferation and the protein production of MyoD in C2C12 cells. Consistent with these findings, in vivo analyses with Ccn2-deficient skeletal muscle showed the decreased PCNA staining and muscle hypoplasia. Furthermore, bone morphogenetic protein (BMP)2-induced Runx2 and Osterix gene expression levels were significantly decreased in C2C12 cells co-treated with CCN2.