Premium
Dedifferentiation and COX‐2 expression is regulated by 2‐deoxy‐D‐glucose by modulating actin cytoskeletal architecture and MAPK pathway in articular chondrocytes
Author(s) -
Mi YU Seon,
Hye LEE Ji,
Kyung YOON Eun,
Ja KIM Song
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a995-a
Subject(s) - chemistry , microbiology and biotechnology , mapk/erk pathway , stress fiber , cytoskeleton , phosphorylation , gene knockdown , chondrocyte , type ii collagen , focal adhesion , cartilage , biology , biochemistry , cell , in vitro , apoptosis , anatomy
2‐deoxy‐D‐glucose(2DG), non‐metabolizable glucose analogue, is known as an inhibitor of glucose transport and glycolysis. In this study, We investigated the effect of 2DG on dedifferentiation and cyclooxygenase‐2(COX‐2) expression in articular chondrocytes. 2DG induced loss of the differentiated phenotype of articular chondrocytes, as demonstrated by the reduction of sulfated proteoglycan accumulation and Type II collagen expression. Taken together, 2DG reduced COX‐2 expression, as determined by the reduction of prostaglandin E2 production and COX‐2 expression. 2DG treatment caused disruption of stress fiber. By using Cytochalasin D(CD) and jasplakinolide(JAS), we show that the actin cytoskeletal architecture is a critical regulator of articular chondrocyte function, including differentiation and inflammatory responses. The addition of CD to 2DG treated chondrocytes blocked the suppressed Type ll collagen and accelerated the inhibition of COX‐2 expression. In contrast, the effects of JAS to 2DG treated chondrocytes accelerated the suppressed Type ll collagen and regained the inhibition of COX‐2 expression. 2DG induced disruption of actin cytoskeletal architecture was associated with paxillin tyrosine protein phosphorylation. Also, 2DG treatment stimulated activation of ERK‐1/2 kinase. Inhibition of ERK‐1/2 with PD 98059 rescued 2DG induced suppression of Type ll collagen and decrease of COX‐2 expression. Our results demonstrated that 2DG dose‐ and time‐ dependently induced dedifferentiation, but suppressed COX‐2 expression via MAPK pathway and paxillin tyrosine phosphorylation.