Chondrogenic potential of IL-10 in mechanically injured cartilage and cellularized collagen ACI grafts.

Abstract

The application of adjunctive mediators in Autologous chondrocyte implantation (ACI) techniques might be useful for improving the dedifferentiated chondrocyte phenotype, to support neocartilage formation and inhibit post-traumatic cartilage destruction. In this study we examined if (a) interleukin 10 treatment can cause chondrogenic phenotype stabilization and matrix preservation in mechanically injured cartilage and if (b) IL-10 can promote chondrogenesis in a clinically applied collagen scaffold for ACI treatment. For (a) bovine articular cartilage was harvested, subjected to an axial unconfined injury and treated with bovine IL-10 (1-10,000pg/ng/ml). For (b) a post-operatively remaining ACI graft was treated with human IL-10. Expression levels of type I/II/X collagen, SOX9 and aggrecan were measured by qPCR (a,b). After 3 weeks cell death was analyzed (nuclear blebbing and TUNEL assay) and matrix composition was determined by GAG measurements and immunohistochemistry (aggrecan, type I/II collagen, hyaluronic acid). One way ANOVA analysis with Bonferroni's correction. (a) IL-10 stabilized the chondrogenic phenotype after injurious compression and preserved matrix integrity. This was indicated by elevated expression of chondrogenic markers COL2A1, ACAN, SOX9, while COL1A1 and COL10A1 were reduced. An increased GAG content paralleled this and histological staining of type 2 collagen, aggrecan and toluidine blue were enhanced after 3 weeks. (b) IL-10 [100pg/ml] improved the chondrogenic differentiation of human chondrocytes, which was accompanied by cartilaginous matrix formation after 3 weeks of incubation. Interleukin-10 is a versatile adjuvant candidate to control the post-injurious environment in cartilage defects and promote chondrogenesis in ACI grafts.