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.
OBJECTIVE
To investigate effects on cartilage metabolism and degeneration of injection of fibronectin fragments (Fn-fs) into rabbit knee joints.


METHODS
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.
Homandberg
G A
GA
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.
Kang
Y
Y
Zhang
J
J
Cole
A A
AA
Williams
J M
JM
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019921:Biotinylation; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism*; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism; D000939:Epitopes; D005353:Fibronectins / Q000008:administration & dosage / Q000494:pharmacology*; D007270:Injections, Intra-Articular; D007719:Knee Joint; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D013194:Staining and Labeling
D000939:Epitopes; D005353:Fibronectins; D009842:Oligopeptides; D010446:Peptide Fragments; D011509:Proteoglycans; C093378:peptide VDIPEN; D000469:Alkaline Phosphatase; D010450:Endopeptidases; D019278:Matrix Metalloproteinase 3; C083641:aggrecanase