Protease inhibitors decrease rabbit cartilage degradation after meniscectomy.
In vitro proteoglycan (PG) synthesis and release were measured on cartilage removed from rabbit knees within 1 week of meniscectomy. Three days following partial lateral meniscectomy, 72% of the femurs and 82% of the tibias had visible ulcers. Cartilage from the weight-bearing areas incorporated 2.0-2.9 times more 35S-sulfate in vitro than cartilage from the opposite, unoperated knees. 3H-thymidine incorporation was 2.5-3.4 times higher for surgical than control groups. 35S-sulfate incorporation by the surgical group was inhibited by 22% in the presence of 10(-4) M U24522, an inhibitor of rabbit chondrocyte metalloprotease (CMP). 3H-thymidine incorporation by the surgical group was inhibited by 28% by 10(-4) M U24522. In vitro PG release from cartilage removed 2 days after surgery was 1.6-3.7 times higher for the surgical than the control group. PG release by the surgical group after 22 h of incubation was reduced to the control level by three CMP inhibitors, U24278, U24279, and U24522. PG release by cartilage from the nonsurgical group was also reduced by these compounds at 22 h. These results suggest that both the anabolic and catabolic processes that are stimulated by surgery can be isolated in vitro and that CMP may be involved in the catabolic process.
Caputo
C B
CB
Department of Pharmacology, Stuart Pharmaceuticals, Division of ICI Americas, Inc., Wilmington, Delaware 19897.
Sygowski
L A
LA
Patton
S P
SP
Wolanin
D J
DJ
Shaw
A
A
Roberts
R A
RA
DiPasquale
G
G
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D008297:Male; D008592:Menisci, Tibial / Q000601:surgery*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D011184:Postoperative Period; D011480:Protease Inhibitors / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis*; D011817:Rabbits; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D011480:Protease Inhibitors; D011509:Proteoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014316:Tritium; D008666:Metalloendopeptidases; D013936:Thymidine