The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1β (IL-1β), 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 hyaluronan (HA) on expression of matrix metalloproteinase-3 (MMP-3), interleukin-1 beta (IL-1 beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in cartilage and synovium during the process of osteoarthritis (OA). Design: Eighteen mature New Zealand white rabbits underwent unilateral anterior 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 second group (no injection group) were not injected after ACLT. At death, 9 weeks following surgery, synovium and cartilage were harvested and total RNA was extracted. Gene expressions, of MMP-3, IL-1 beta and TIMP-1 were analyzed 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 expression 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.