IN-VIVO EFFECTS OF STROMELYSIN ON THE COMPOSITION AND PHYSICAL-PROPERTIES OF RABBIT ARTICULAR-CARTILAGE IN THE PRESENCE AND ABSENCE OF A SYNTHETIC INHIBITOR

Objective. To characterize the effects of intraarticular injection of recombinant human stromelysin (SLN) on the matrix composition and phys ical properties of cartilage from lapine stifle joints and the modulat ion of these effects by the systemic administration of an N-carboxyalk yl synthetic matrix metalloproteinase inhibitor, L-696,418. Methods. F emale 6-8-week-old New Zealand white rabbits received an intraarticula r injection of 100 Erg activated SLN in 1 stifle joint and buffer in t he contralateral control knee; these animals were killed after 1 hour. A separate group of animals received an intravenous injection of eith er 30 mg/kg L-696,418 or buffer prior to intraarticular injection of S LN, Joints were dissected and analyzed for proteoglycan (PG) loss into joint fluid, tissue biochemical composition, and histology by toluidi ne blue or anti-VDIPEN antibody staining, or were frozen for physical property analysis. Disks of femoropatellar groove cartilage were harve sted from the stipe joint and tested in uniaxially confined compressio n for determination of electromechanical and mechanical properties. Re sults. Lapine stifle joints that received injection of SLN without sys temic administration of L-696,418 showed a 13-fold increase in loss of PG into synovial fluid, Cartilage from these joints showed significan t decreases in streaming potential at 1 Hz and electrokinetic coupling coefficient, but no change in equilibrium modulus, dynamic stiffness, or hydraulic permeability. Systemic treatment with L-696,418 resulted in a significant decrease in loss of PG into joint fluid and eliminat ion of changes in cartilage high-frequency streaming potential and cou pling coefficient in joints that were injected with SLN. Conclusion. T he 1-hour exposure to SLN in vivo resulted in loss of PG and exposure of the VDIPEN epitope of the aggrecan core protein in the superficial region of the tissue near the articular surface, This highly localized degradation resulted in electromechanical behavior changes, but littl e or no change occurred in mechanical properties. Systemic administrat ion of L-696,418 significantly decreased loss of PG from cartilage and prevented the highly localized tissue degradation and the resultant c hanges in electromechanical behavior caused by intraarticular SLN inje ction.