Pathological mechanism of osteoarthritis -analysis of molecules responsing to mechanical stress-

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In the next step, the expression of GADD45beta was examined using immunohistochemistry of articular cartilage from human and animal samples.GADD45beta was especially highly expressed in cluster of early OA cartilage in human reticular cartilage. The hypertrophic chondrocyte were positive in OA animal model but not in normal animal. These findings suggested GADD45beta functions to support the mechanism of dedifferentitation of chondrocyte during the process of OA.To examine the mechanical function of GADD45beta in terms of phenotype of chondrocyte, luciferase assay and real time PCR were performed using chondrocyte cell line. Interestingly, type X collagen and MMP-13 gene expressions were increased by GADD45beta over-expression, but decreased by GADD45beta suppressing using siRNA. Additionally, type II collagen gene expression was decreased by by GADD45beta over-expression and increased by by GADD45beta suppressing. We also investigated apoptosis analysis using ATDC5 cells. GADD45beta clearly functioned anti-apoptotic way.This protein accelerates Type X collagen and MMP-13 gene expression and suppresses Type II collagen gene expression. GAdd45beta also noble function in terms of anti-apoptosis in chondrocyte in vitro.These results suggest the importance of GADD45beta function in OA to support the survival of chondrocytes during the process of OA, resulting in dedifferentiation from normal chondrocyte.