PMID- 11795986 OWN - NLM STAT- MEDLINE DCOM- 20020311 LR - 20161018 IS - 1063-4584 (Print) IS - 1063-4584 (Linking) VI - 9 IP - 8 DP - 2001 Nov TI - A single injection of fibronectin fragments into rabbit knee joints enhances catabolism in the articular cartilage followed by reparative responses but also induces systemic effects in the non-injected knee joints. PG - 673-83 AB - OBJECTIVE: To investigate effects on cartilage metabolism and degeneration of injection of fibronectin fragments (Fn-fs) into rabbit knee joints. DESIGN: The knees of adolescent New Zealand white rabbits were intraarticularly injected with rabbit Fn-fs. Cartilage sections from both injected and non-injected joints were treated with Safranin-O, with antibodies to the VDIPEN and NITEGE neoepitopes of degraded aggrecan and to matrix metalloproteinase-3 (MMP-3). Proteoglycan (PG) content of cartilage was measured by a dimethylmethylene blue assay of papain digests. PG synthesis rates were measured by(35)S-sodium sulfate incorporation into explanted cartilage. RESULTS: In the injected joint cartilage, the Fn-fs bound cells in the upper superficial zone maximally between 6 and 24 h. By day 2, MMP-3 protein was enhanced and cartilage PG content and PG synthesis rates were reduced 40% and 70%, respectively. MMP-3 epitope and VDIPEN and NITEGE neoepitopes were also enhanced. The PG content then increased to supernormal levels from days 14 to 35 and then declined to normal levels by day 70, as did PG synthesis rates. In the non-injected joint cartilage, Fn-fs were not detected. Although MMP-3 expression was enhanced between days 2 and 21 as well as VDIPEN neoepitope, the PG content was never reduced but rather enhanced to supernormal levels from days 21 to 35. This was associated with enhanced PG synthesis by day 7, which decreased to control levels by day 70. CONCLUSIONS: In this cartilage degeneration model, loss of cartilage PG is followed by supernormal anabolic responses that facilitate PG restoration. Further, the damage causes a systemic effect of enhanced PG synthesis and content in the non-injected joint cartilage. CI - Copyright 2001 OsteoArthritis Research Society International. FAU - Homandberg, G A AU - Homandberg GA AD - Department of Biochemistry, Section of Rheumatology, Rush Medical College at Rush-Presbyterian-St Luke's Medical Center, 1653 West Congress Parkway, Chicago, Illinois 60612-3864, USA. FAU - Kang, Y AU - Kang Y FAU - Zhang, J AU - Zhang J FAU - Cole, A A AU - Cole AA FAU - Williams, J M AU - Williams JM LA - eng GR - AR39293-03/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Osteoarthritis Cartilage JT - Osteoarthritis and cartilage JID - 9305697 RN - 0 (Epitopes) RN - 0 (Fibronectins) RN - 0 (Oligopeptides) RN - 0 (Peptide Fragments) RN - 0 (Proteoglycans) RN - 0 (peptide VDIPEN) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - EC 3.4.- (Endopeptidases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.99.- (aggrecanase) SB - IM MH - Alkaline Phosphatase/metabolism MH - Animals MH - Biotinylation MH - Blotting, Western MH - Cartilage, Articular/*metabolism MH - Densitometry MH - Dose-Response Relationship, Drug MH - Endopeptidases/metabolism MH - Epitopes MH - Fibronectins/administration & dosage/*pharmacology MH - Injections, Intra-Articular MH - Knee Joint MH - Male MH - Matrix Metalloproteinase 3/metabolism MH - Oligopeptides/metabolism MH - Peptide Fragments/metabolism MH - Proteoglycans/metabolism MH - Rabbits MH - Staining and Labeling EDAT- 2002/02/14 10:00 MHDA- 2002/03/12 10:01 CRDT- 2002/02/14 10:00 PHST- 2002/02/14 10:00 [pubmed] PHST- 2002/03/12 10:01 [medline] PHST- 2002/02/14 10:00 [entrez] AID - S1063-4584(01)90419-4 [pii] AID - 10.1053/joca.2001.0419 [doi] PST - ppublish SO - Osteoarthritis Cartilage. 2001 Nov;9(8):673-83. doi: 10.1053/joca.2001.0419.