Involvement of p38 MAPK in regulation of MMP13 mRNA in chondrocytes in response to surviving stress to endoplasmic reticulum

被引：46

作者：

Hamamura, Kazunori ^{[1
,2
]}

Goldring, Mary B. ^{[3
]}

Yokota, Hiroki ^{[1
,2
]}

机构：

[1] Indiana Univ Purdue Univ, Dept Biomed Engn, Indianapolis, IN 46202 USA

[2] Indiana Univ Purdue Univ, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA

[3] Hosp Special Surg, New York, NY 10021 USA

来源：

ARCHIVES OF ORAL BIOLOGY | 2009年 / 54卷 / 03期

关键词：

Chondrocytes; ER stress; MMP13; p38; MAPK; MATRIX-METALLOPROTEINASE; 13; OSTEOARTHRITIS-LIKE CHANGES; PERK EIF2-ALPHA KINASE; GENE-EXPRESSION; ARTICULAR CHONDROCYTES; COLLAGENASE; KAPPA-B; APOPTOSIS; DIFFERENTIATION; ACTIVATION;

D O I：

10.1016/j.archoralbio.2008.11.003

中图分类号：

R78 [口腔科学];

学科分类号：

1003 ;

摘要：

MMP13 is enriched in mature chondrocytes and considered a prime cause of ECM degradation in the osteoarthritic articular cartilage in temporomandibular joints. We asked whether surviving stress to the endoplasmic reticulum (ER) would upregulate transcription of MMP13, and if so, whether a cross-talk would exist between surviving ER stress and p38 MAPK pathways. Using C28/12 chondrocyte cell line, ER stress was induced by thapsigargin and tunicamycin and upregulation of phosphorylated eIF2 alpha and ATF4 protein was observed. Both thapsigargin and tunicamycin elevated the mRNA level of MMP13 and phosphorylation of p38 MAPK. Thapsigargin-induced MMP13 mRNA upregulation was significantly suppressed by SB203580, while its upregulation by tunicamycin was completely attenuated by SB203580. Those results support that homeostasis of chondrocytes is affected by the surviving ER stress through p38 MAPK pathways, suggesting a potential role of ER stress in joint diseases such as osteoarthritis. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：279 / 286

页数：8

共 33 条

[31] Multiple signals induce endoplasmic reticulum stress in both primary and immortalized chondrocytes resulting in loss of differentiation, impaired cell growth, and apoptosis [J].