Abstract
The purpose of this study was to examine how chondrocytes are involved in the molecular mechanism of inflammation in rheumatoid arthritis (RA). A chondrosarcoma cell line (OUMS-27) was cultured and treated with interleukin-1beta (IL-1beta). Changes in the expression levels of matrix metalloproteinase-1 (MMP-1), metalloproteinase-13 (MMP-13), and gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) were assessed by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays. IL-1beta induced the expressions of MMP-1, MMP-13, and GLS mRNAs and proteins in a dose-dependent manner. Selective inhibition of the p38 mitogen-activated protein kinase (p38 MAPK) pathway with SB 203580 and SB 202190 blocked the expression of MMP-1, MMP-13, and GLS more strongly than selective in hibition of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway by PD 98059. These findings suggest that chondrocytes may intensify cartilage destruction and inflammation in RA by the induction of MMP-1, MMP-13, and GLS by IL-1beta and that the p38 MAPK pathway plays an important role in these inductions.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Base Sequence
-
Chondrosarcoma / pathology
-
Chondrosarcoma / physiopathology
-
Collagenases / drug effects
-
Collagenases / genetics*
-
Dose-Response Relationship, Drug
-
Enzyme-Linked Immunosorbent Assay
-
Gene Expression / physiology
-
Humans
-
Interleukin-1 / metabolism*
-
Interleukin-1 / pharmacology
-
Matrix Metalloproteinase 1 / drug effects
-
Matrix Metalloproteinase 1 / genetics*
-
Matrix Metalloproteinase 13
-
Mitogen-Activated Protein Kinase 1 / metabolism
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases / antagonists & inhibitors
-
Mitogen-Activated Protein Kinases / metabolism*
-
Molecular Sequence Data
-
RNA, Messenger / analysis
-
Reference Values
-
Reverse Transcriptase Polymerase Chain Reaction
-
Sensitivity and Specificity
-
Thymidine Phosphorylase / drug effects
-
Thymidine Phosphorylase / genetics*
-
Thymidine Phosphorylase / metabolism
-
Tumor Cells, Cultured
-
p38 Mitogen-Activated Protein Kinases
Substances
-
Interleukin-1
-
RNA, Messenger
-
Thymidine Phosphorylase
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases
-
p38 Mitogen-Activated Protein Kinases
-
Collagenases
-
MMP13 protein, human
-
Matrix Metalloproteinase 13
-
Matrix Metalloproteinase 1