PMID- 10222217 OWN - NLM STAT- MEDLINE DCOM- 19990615 LR - 20220317 IS - 1063-4584 (Print) IS - 1063-4584 (Linking) VI - 7 IP - 2 DP - 1999 Mar TI - The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1beta(IL-1beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis. PG - 182-90 AB - OBJECTIVE: To assess the influence of intra-articular injection of hyaluronan (HA) on expression of matrix metalloproteinase-3 (MMP-3), interleukin-1beta(IL-1beta), 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 ml 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-1beta and TIMP-1 were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) 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-1beta 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-1beta expression in synovium at a progressed grade. No effect of HA 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-1beta in synovium during early development of OA. CI - Copyright 1999 OsteoArthritis Research Society International. FAU - Takahashi, K AU - Takahashi K AD - Department of Orthopaedics, University of California San Diego-School of Medicine, 9500 Gilman Dr., La Jolla, CA, 92093-0630, USA. FAU - Goomer, R S AU - Goomer RS FAU - Harwood, F AU - Harwood F FAU - Kubo, T AU - Kubo T FAU - Hirasawa, Y AU - Hirasawa Y FAU - Amiel, D AU - Amiel D LA - eng GR - AG07996/AG/NIA NIH HHS/United States GR - AR07484/AR/NIAMS NIH HHS/United States GR - AR28467/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Osteoarthritis Cartilage JT - Osteoarthritis and cartilage JID - 9305697 RN - 0 (Interleukin-1) RN - 0 (RNA, Messenger) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 9004-61-9 (Hyaluronic Acid) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Anterior Cruciate Ligament/drug effects/metabolism MH - Down-Regulation/*drug effects MH - Hyaluronic Acid/*pharmacology MH - Interleukin-1/*biosynthesis/genetics MH - Matrix Metalloproteinase 3/biosynthesis/*drug effects/genetics MH - Osteoarthritis, Knee/*metabolism/pathology MH - RNA, Messenger/genetics MH - Rabbits MH - Reverse Transcriptase Polymerase Chain Reaction MH - Synovial Membrane/metabolism MH - Tissue Inhibitor of Metalloproteinase-1/biosynthesis/*drug effects/genetics EDAT- 1999/05/01 00:00 MHDA- 1999/05/01 00:01 CRDT- 1999/05/01 00:00 PHST- 1999/05/01 00:00 [pubmed] PHST- 1999/05/01 00:01 [medline] PHST- 1999/05/01 00:00 [entrez] AID - S1063-4584(98)90207-2 [pii] AID - 10.1053/joca.1998.0207 [doi] PST - ppublish SO - Osteoarthritis Cartilage. 1999 Mar;7(2):182-90. doi: 10.1053/joca.1998.0207.