• Chondrocytes
• Osteoarthritis
• Arthritis, Experimental

The recent publication in the Annals of Rheumatic Diseases by Zhang et al 1 ‘Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7’ includes conclusions that ‘inhibition of JNK activity ameliorated chondrocyte senescence and cartilage degeneration’ and ‘this study suggests that targeting FBXW7–MKK7–JNK signalling may be a novel therapeutic approach for osteoarthritis (OA) treatment’. We were surprised to see these conclusions since we found very different results in a recent study2 examining the role of JNK signalling in OA. In that study, rather than using a chemical inhibitor that can have off-target effects, as was done in the Zhang et al study,1 we evaluated JNK knockout mice in both the DMM model of OA performed at 12 weeks of age and in the model of naturally occurring age-related OA at 18 months of age. We conducted a well-powered study with 15 mice per experimental group and extensive, blinded, histologic assessment of OA with outcome measures of cartilage damage, osteophytes and synovial hyperplasia, as well as histomorphometric measures of cartilage and subchondral bone. We did not find any reduction in OA severity in JNK1, JNK2 or JNK1/2 double knockout mice in the DMM model, while in 18-month old mice with spontaneous OA, we noted more severe OA in JNK1 and JNK2 single knockouts (we did not …