Background and objectives Osteoarthritis (OA) is a degenerative joint disease characterised by severe cartilage destruction, with a putative role for synovial macrophages. Recently it has become clear that over 50% of the patients also show low grade joint inflammation reflected by a thickened synovial lining and elevated production of cytokines like interleukin-1 (IL-1)by different cell types in the synovium. IL-1 mediates cartilage destruction by degrading existing proteoglycans and inhibiting new formation ofproteoglycans by stimulating degradative enzyme production. However, treatment of OA patients with IL-1 inhibitors has so far been disappointing. In this study we investigated the role of IL-1α/β in synovitis and cartilage destruction during experimental collagenase-induced OA (CiOA).
Materials and methods Experimental OA was induced by intra-articular injection of collagenase into WT and IL-1αβ-/- mice. At day 7 after CiOA induction, total knee joints were stained with haematoxylin/eosin (H&E) to score synovial activation (arbitrary score from 0–3). Cartilage destruction at day 7 and 42 after induction of CiOA was determined in knee sections stained with safranin O/fast green using a modified Pritzker score. Gene expression in inflamed synovium was analysed using qPCR with primers for several pro- and anti-inflammatory cytokines.
Results Synovitis in IL-1αβ-/- mice at day 7 of CiOAwas not different from WT controls (2.9 ± 0.2 and 2.7 ± 0.4 respectively). Absence of IL-1α/β had no effect on synovial mRNA levels of pro-inflammatory mediators KC, S100A8 and S100A9. IL-6 mRNA levels, however, were significantly down-regulated in the synovium of IL-1αβ-/- mice (3-fold reduction). The lack of IL-1α/β also did not affect gene expression of anti-inflammatory cytokines IL-10, TGFβ and iNOS. Cartilage destruction in CiOA clearly aggravated over time. Cartilage lesions in IL-1αβ-/- mice were not significantly different from WT controls at day 7. Also no difference in cartilage damage was measured at day 42 of CiOA when compared to WT (at the medial femur (95.3 ± 42.0 vs. 65.5 ± 54.5), medial tibia (84.5 ± 36.6 vs. 55.1 ± 38.9), lateral femur (69.6 ± 43.9 vs. 60.8 ± 35.8), and lateral tibia (49.8 ± 26.3 vs. 55.4 ± 17.1)).
Conclusions IL-1β does not affect synovial inflammation nor cartilage destruction during collagenase-induced osteoarthritis, implicating that other macrophage-derived mediators are responsible for the joint damage.
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