[Effects of intra-articular injection of p38 mitogen-activated protein kinase inhibitor on matrix metalloproteinase in articular cartilage of a rat model of osteoarthritis]

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2007 Dec;29(6):777-81.
[Article in Chinese]

Abstract

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).

Conclusion: SB203580 can inhibit the expressions of MMP-3 and MMP-13 and thus protect the cartilage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / enzymology*
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology*
  • Imidazoles / therapeutic use
  • Injections, Intra-Articular
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinases, Secreted / metabolism*
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / enzymology
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / administration & dosage
  • Pyridines / pharmacology*
  • Pyridines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

  • Imidazoles
  • Protein Kinase Inhibitors
  • Pyridines
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinases, Secreted
  • Matrix Metalloproteinase 3
  • SB 203580