Transforming Growth Factor-β Stimulates Articular Chondrocyte Cell Growth through p44/42 MAP Kinase (ERK) Activation

Endocrine Journal

MAKOTO OSAKI²  HIROYUKI SHINDO²  TOMOKO MATSUMOTO²  YOUICHI MIYAZAKI²  YASUHIRO HIROTA²  AKIHIKO YONEKURA²  SHUNICHI YAMASHITA¹  AKIRA OHTSURU¹  HIROYUKI NAMBA¹  TOMOO TSUKAZAKI¹ 

[1] Department of Nature Medicine, Atomic Bomb Disease Institute, Nagasaki University School of Medicine;Department of Orthopedic Surgery, Nagasaki University School of Medicine

关键词: TGF-β1;    Articular chondrocyte;    Cell growth;    MAPK;    ERK;   

DOI  :  10.1507/endocrj.46.545

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(25)Cited-By(26)Transforming growth factor-β1 (TGF-β1) stimulates articular chondrocyte cell proliferation and extracellular matrix formation. We reported previously that immediate and transient expression of c-fos mRNA through protein kinase C activation is required for the mitogenic effect of TGF-β1 on cultured rat articular chondrocytes (CRAC). In gel kinase assays using myelin basic protein (MBP) showed that total cell lysates from cells treated with TGF-β1 caused rapid phosphorylation of MBP, which suggests the involvement of mitogen-activated protein kinase (MAPK) activation. To identify specific MAPK pathways activated by TGF-β1, we performed in vitro kinase assays using specific substrates. TGF-β1 induced a rapid activation of extracellular signal regulated kinase (ERK) with a peak at 5min, which decreased to basal levels within 240min after TGF-β1 stimulation. In contrast, the c-jun N-terminal kinase activity increased only about 2.5-fold after 240min of stimulation and p38 MAPK activity did not change significantly. ERK activation by TGF-β1 was also confirmed by in vivo phosphorylation assays of Elk1. However, a specific MEK1 inhibitor, PD98059, significantly decreased TGF-β1 induced Elk1 phosphorylation in a dose-dependent manner. Furthermore, PD98059 reduced the TGF-β1-induced cell growth by 40%. These results indicate that TGF-β1 specifically activates MEK1 and subsequent ERK pathways in CRAC, and that the activation of this MAPK pathway plays a role in the mitogenic response to TGF-β1.

【 授权许可】

Unknown