• Osteoarthritis
• Arthritis
• Chondrocytes

In January 2022, we reported an important role for FBXW7 in the association between mechanical overloading, chondrocyte senescence and cartilage ageing in the pathology of osteoarthritis (OA).1 Our data support the idea that JNK signalling pathway is activated in OA, and DTP3 can inhibit JNK in chondrocytes.1 Two of our observations have been challenged by Dr. Richard F. Loeser and Dr. Philip R. Coryell. We thank Dr. Loeser and Dr. Coryell for their thoughtful correspondence. While their comments have promoted us to take another critical look at our data and interpretations, we think that their remarks and the associated results do not alter our conclusions. We believe that our published study1 accurately depicts the role of FBXW7 in mechanical overloading and OA development.

JNK signalling is a highly complex signalling pathway and has been shown to be activated (phosphorylated) in OA.2 3 Accumulating evidence now also suggests that JNK can play a key role in OA-related cartilage destruction (table 1).2–20 Specifically, a number of JNK inhibitors have been used in both in vitro and in vivo studies, which concluded that inhibition of JNK signalling has a protective effect on OA. For example, studies reported by Dr. Lu et al, Dr. Zhang et al, Dr. Kang et al and Dr. Cherifi et al supported that use of SP600125, a JNK-specific inhibitor, as a disease-modifying anti-OA drug.3–6 Furthermore, the protective effect of JNK inhibition on OA has also been confirmed by using a knockout mouse model of JNK. Dr. Jeremy Saklatvala and colleagues found that …