Interleukin-37 Ameliorates Articular Cartilage Damage in Two Murine Models of Osteoarthritis

ObjectiveIn this study, we investigated whether interleukin (IL)-37 ameliorates experimental osteoarthritis (OA).MethodsThe effects of IL-37 were investigated in collagenase-induced OA (CiOA) and destabilization of the medial meniscus (DMM). Human IL-37-adenovirus (ad-IL-37) was injected into the affected knee joint 4 and 18 days after the induction of OA. Luciferase-adenovirus was injected as control. Mice were sacrificed for histology at early and late stage of OA development. Interleukin-37 protein expression was confirmed by immunohistochemistry. Cartilage damage, osteophyte size and joint capsule thickness were measured. The effectiveness of ad-IL-37 was confirmed in vitro in human OA fibroblasts using real-time qualitative polymerase chain reaction (RT-qPCR) and Western blotting.ResultsInterleukin-37 protein expression was visible for at least 7 days after injection. At day 28, 10 days after the second injection, no clear synovial IL-37 staining was found any more, in both models. At day 28 of CiOA, ad-IL-37 significantly reduced articular cartilage damage and this was still reduced, although not significantly, at the late time point (day 42). In the DMM model, significant beneficial effect of IL-37 on cartilage damage was found at the late time point. In both OA models ad-IL-37 injections reduced the size of osteophytes.ConclusionInterleukin-37 ameliorated OA-induced articular cartilage damage and osteophyte formation in both models.