tailieunhanh - Báo cáo Y học: CTGF/Hcs24 induces chondrocyte differentiation through a p38 mitogen-activated protein kinase (p38MAPK), and proliferation through a p44/42 MAPK/extracellular-signal regulated kinase (ERK)

Connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24) promotes proliferation and differentiation of chondrocytes in culture. We investigated the roles of two major types of mitogen activated protein kinase (MAPK) in the promotion of proliferation and differentiation by CTGF/Hcs24. Here we report the effects of the MAPKK/MEK 1/2 inhibitor, PD098059, and p38 MAPK inhibitor, SB203580, in a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8) and rabbit growth cartilage (RGC) cells treated with CTGF/ Hcs24 | Eur. J. Biochem. 268 6058-6065 2001 FEBS 2001 CTGF Hcs24 induces chondrocyte differentiation through a p38 mitogen-activated protein kinase p38MAPK and proliferation through a p44 42 MAPK extracellular-signal regulated kinase ERK Gen Yosimichi1 2 Tohru Nakanishi1. Takashi Nishida1 3 Takako Hattori1. Teruko Takano-Yamamoto2 and Masaharu Takigawa1 3 1 Department of Biochemistry and Molecular Dentistry and department of Orthodontics Okayama University Graduate School of Medicine and Dentistry Okayama Japan 3Biodental Research Center Okayama University Dental School Japan Connective tissue growth factor hypertrophic chondrocyte specific gene product 24 CTGF Hcs24 promotes proliferation and differentiation of chondrocytes in culture. We investigated the roles of two major types of mitogen activated protein kinase MAPK in the promotion of proliferation and differentiation by CTGF Hcs24. Here we report the effects of the MAPKK MEK 1 2 inhibitor PD098059 and p38 MAPK inhibitor SB203580 in a human chondrosarcoma-derived chondrocytic cell line HCS-2 8 and rabbit growth cartilage RGC cells treated with CTGF Hcs24. In the proliferation phase CTGF Hcs24 induced a fivefold increase in the phosphorylation of p44 42 MAPK ERK and a twofold increase in that of p38 MAPK in an in vivo kinase assay. These inhibitors of MAPKK and MAPK suppressed phosphorylation of ets-like gene-1 Elk-1 and nuclear activating transcription factor-2 Atf-2 induced by CTGF Hcs24 in a dose-dependent manner respectively. Western blot analysis showed that phosphorylation of ERK was induced from 30 to 60 min and phosphorylation of p38 MAPK from 10 to 15 min after the addition of CTGF Hcs24 in confluence HCS-2 8 cells. PD098059 suppressed the DNA synthesis of HCS-2 8 cells and RGC cells while SB203580 did not. On the other hand the p38 MAPK inhibitor SB203580 completely inhibited the CTGF Hcs24-induced synthesis of proteoglycans in HCS-2 8 cells and RGC cells but the MEK1 2 inhibitor PD098059 did not. These .

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