The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1 beta (IL-1 beta), and tissue inhibitor of metalloproteinase-1(TIMP-1) gene expression during the development of osteoarthritis

Objective: To assess the influence of intra-articular injection of hyaluron an (HA) on expression of matrix metalloproteinase-3 (MMP-3), interleukin-1 beta (IL-1 beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in c artilage and synovium during the process of osteoarthritis (OA). Design: Eighteen mature New Zealand white rabbits underwent unilateral ante rior cruciate ligament transection (ACLT) and were divided into two groups. The first group (HA injection group) received 0.3 mi of intra-articular HA injections into the ACLT knees 4 weeks after transection, once a week for 5 weeks as per clinical treatment presently utilized. The animals in the se cond group (no injection group) were not injected after ACLT. At death, 9 w eeks following surgery, synovium and cartilage were harvested and total RNA was extracted. Gene expressions, of MMP-3, IL-1 beta and TIMP-1 were analy zed using reverse transcription-polymerase chain reaction (RT-PGR) for each subgroup created according to morphological grade of OA. Results: The extent and grade of cartilage damage in the HA injection group was less severe than in the no injection group. In synovium, expression of MMP-3 and IL-1 beta mRNA was suppressed in the mild grades of OA in the HA injection group. HA treatment had either no effect on MMP-3 expression in cartilage at all grades of OA or on enhanced MMP-3 and IL-1 beta expression in synovium at a progressed grade. No effect of EIA treatment on TIMP-1 ex pression was observed in either cartilage or synovium. Conclusions: These results suggest that one of the mechanism of therapeutic effect of HA is down-regulation of MMP-3 and IL-1 beta in synovium during early development of OA.