[Effects of intra-articular injection of p38 mitogen-activated protein kinase inhibitor on matrix metalloproteinase in articular cartilage of a rat model of osteoarthritis].
OBJECTIVE
To observe the effect of intra-articular injection of SB203580, a selective p38 mitogen-activated protein kinase inhibitor, on the expression of matrix metalloproteinase (MMP)-3, MMP-13 in a rat model of osteoarthritis (OA) and to explore the relationship between the MMP-3/MMP-13 expressions and the severity of OA.


METHODS
Fourty SD rats underwent unilateral anterior cruciate ligament transection (ACLT) and then randomly divided into four groups, with 10 rats in each group. Group A received 0.1 ml intra-articular injection of SB203580 at a high concentration of 100 micromol/L (once a week) immediately after surgery, and group B were treated under the same condition using SB203580 with a low concentration of 10 micromol/ L Group C received 0.1 ml intra-articular normal saline, and group D were not injected as controls after ACLT. All rats were sacrificed seven weeks after the surgery. Macroscopic and immunohistochemical studies were performed on the cartilage. Protein expressions of MMP-3 and MMP-13 were determined by Western blot. RESULTS Cartilage degradation was significantly milder in group A and group B than in the control groups, as shown by morphological studies (P < 0. 05) and immunohistochemical studies (P < 0. 05). The protein expressions of MMP-3 and MMP-13 in cartilage were significantly lower in groups A and B than in groups C and D (P < 0.01).


CONCLUSIONS
SB203580 can inhibit the expressions of MMP-3 and MMP-13 and thus protect the cartilage.
Chen
Wei-Dong
WD
Center of Diagnosis and Treatment for Joint Disease, Nanjing Gulou Hospital, Medical School of Nanjing University, Nanjing 210008, China.
Jiang
Qing
Q
Chen
Dong-Yang
DY
Xu
Hua
H
Zhang
Ya-Feng
YF
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13; D053505:Matrix Metalloproteinases, Secreted; D019278:Matrix Metalloproteinase 3; C093642:SB 203580