Effect of dehydroepiandrosterone on mRNA expression of MMP-3, TIMP-1 and IL-1β in the cartilage and synovium of rabbits with osteoarthritis

Objective To observe the effects of intra-articular injection of dehydroepiandrosterone (DHEA) on mRNA expression of metalloproteinases-3 (MMP-3)tissue inhibitor of metalloproteinases-1 (TIMP-1) and interleukin-1beta ( IL-1β) in the cartilage and synovium of rabbits with osteoarthritis. Methods Twenty New Zealand rabbits underwent unilateral anterior cruciate ligament resection and were divided into two groups. The animals in experimental group were injected in the knees with 100 μmol/L DHEA in dimethylsulphoxide 4 weeks after resection, once a week for five weeks. Rabbits in the control group were treated under the same condition using dimethylsulphoxide. All rabbits were sacrificed 9 weeks after operation and the knee joints were examined by gross morphology. The mRNA expression of MMP-3, TIMP-1 and IL-1β in the cartilage and synovium was analyzed using reverse transcription polymerase chain reaction. Results Gross morphologic inspection showed that the extent of cartilage and synovium damage in the experimental group were less severe than in the control group. The expression of MMP-3 mRNA in cartilage and synovium was significantly decreased (both P0.05), while the expression of TIMP-1 mRNA was significantly increased in the experimental group compared with that in the control group (both P0.05). No significant difference of IL-1βmRNA expression in the cartilage was found between the experimental and control group (P0.05), however it was significantly suppressed in experimental group compared with control group(P0.01). Conclusion DHEA can inhibit the progression of osteoarthritis in the experimental model. Down-regulation of MMP-3 and up-regulation of TIMP-1 in cartilage and synovium and down-regulation of IL-1β in the synovium may be the mechanism of protective effect of DHEA on osteoarthritis.