IL-10 reduces apoptosis and extracellular matrix degradation after injurious compression of mature articular cartilage

Abstract

Objective: The aim of this study was to examine whether anti-inflammatory interleukin-10 (IL-10) exerts chondroprotective effects in an in vitro model of a single mechanical injury of mature articular cartilage.

Method: Articular cartilage was harvested from the femoro-patellar groove of adult cows (Bos taurus) and cultured w/o bovine IL-10. After 24 h of equilibration explants were subjected to an axial unconfined compression (50% strain, velocity 2 mm/s, held for 10 s). After 96 h cell death was measured histomorphometrically (nuclear blebbing, NB) and the release of glycosaminoglycans (GAG, DMMB assay) and nitric oxide (NO, Griess-reagent) were analyzed. mRNA levels of matrix degrading enzymes and nitric oxide synthetase were measured by quantitative real time PCR. Differences between groups were calculated using a one-way ANOVA with a Bonferroni post hoc test.

Results: Injurious compression significantly increased the number of cells with NB, release of GAG and nitric oxide and expression of MMP-3, -13, ADAMTS-4 and NOS2. Administration of IL-10 significantly reduced the injury related cell death and release of GAG and NO, respectively. Expression of MMP-3, -13, ADAMTS-4 and NOS2 were significantly reduced.

Conclusion: Joint injury is a complex process involving specific mechanical effects on cartilage as well as induction of an inflammatory environment. IL-10 prevented crucial mechanisms of chondrodegeneration induced by an injurious single compression. IL-10 might be a multipurpose drug candidate for the treatment of cartilage-related sports injuries or osteoarthritis (OA).

Keywords: Cartilage; IL-10; Injurious compression; Osteoarthritis.