PMID- 11399096 OWN - NLM STAT- MEDLINE DCOM- 20010621 LR - 20161018 IS - 1063-4584 (Print) IS - 1063-4584 (Linking) VI - 9 IP - 4 DP - 2001 May TI - Differential regulation of gelatinases by transforming growth factor beta-1 in normal equine chondrocytes. PG - 325-31 AB - OBJECTIVE: Cartilage destruction in osteoarthritis (OA) is associated with increased levels of several matrix metalloproteinases (MMPs), including the gelatinases MMP-2 and MMP-9. While increases in some MMPs may be destructive, up-regulation of others may result from increases in normal tissue turnover. The production of MMP-2 and MMP-9 by the anabolic transforming growth factor beta-1 (TGF-beta1) in normal equine chondrocytes was investigated. DESIGN: Equine chondrocytes from clinically normal femoropatellar joints were maintained in alginate beads. After serum deprivation, cells were exposed to TGF-beta1 at several concentrations for varying times. Activities of MMP-2 and MMP-9 were estimated by gelatin zymography, while mRNA for MMP-2, MMP-9 and collagen type II were detected using reverse transcription-polymerase chain reaction. RESULTS: Stimulation with TGF-beta1 differentially regulated MMP-2 and MMP-9, with strong up-regulation of both MMP-9 mRNA and enzyme. Increases in MMP-9 enzyme were dose-dependent (0-49 h). There is some evidence suggesting a slight reduction in MMP-2 release following stimulation. Collagen type II mRNA was transiently increased following stimulation. CONCLUSIONS: The different effects of TGF-beta1 on MMP-2 and MMP-9 production by normal chondrocytes suggests different roles for these enzymes. The increases in both MMP-9 and collagen type II mRNA following stimulation may suggest a role for MMP-9 in tissue maintenance. Therefore, increased MMP-9 may be secondary to, as distinct from a cause of, cartilage damage. CI - Copyright 2001 OsteoArthritis Research Society International. FAU - Thompson, C C AU - Thompson CC AD - Connective Tissue Research Group, Faculty of Veterinary Science, University of Liverpool, Liverpool, L69 3BX, UK. FAU - Clegg, P D AU - Clegg PD FAU - Carter, S D AU - Carter SD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Osteoarthritis Cartilage JT - Osteoarthritis and cartilage JID - 9305697 RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 9007-34-5 (Collagen) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Cartilage/*metabolism MH - Chondrocytes/*physiology MH - Collagen/metabolism MH - Hindlimb MH - Horses MH - Joints MH - Matrix Metalloproteinase 2/*biosynthesis MH - Matrix Metalloproteinase 9/*biosynthesis MH - RNA, Messenger/metabolism MH - Transforming Growth Factor beta/*pharmacology EDAT- 2001/06/12 10:00 MHDA- 2001/06/22 10:01 CRDT- 2001/06/12 10:00 PHST- 2001/06/12 10:00 [pubmed] PHST- 2001/06/22 10:01 [medline] PHST- 2001/06/12 10:00 [entrez] AID - S1063-4584(00)90392-3 [pii] AID - 10.1053/joca.2000.0392 [doi] PST - ppublish SO - Osteoarthritis Cartilage. 2001 May;9(4):325-31. doi: 10.1053/joca.2000.0392.