Prof. Kingston Mak recently published a paper in the journal Annals of the Rheumatic Diseases depicting the functions of Wnt16 during osteoarthritis progression. This work was in collaboration with Prof. Ling Qin from the Chinese University of Hong Kong. The study “Wnt16 attenuates osteoarthritis progression through a PCP/JNK-mTORC1-PTHrP cascade” by Tong and Zeng et al. provides new evidence showing that Wnt16 regulates chondrocyte differentiation both in skeletal development and articular cartilage homeostasis.
They found that Wnt16 inhibits chondrocyte hypertrophy in the growth plates as well as articular cartilage. By genetic and surgically induced mouse models analyses, they showed that Wnt16 deficiency further exaggerates OA progression. Intra-articular injection of Wnt16 adenovirus attenuates cartilage degradation. Cellular and molecular analyses demonstrate that Wnt16 mainly activates the non-canonical PCP/JNK pathway and subsequently induces PTHrP expression mediated by mTORC1 in regulating chondrocyte hypertrophy. More importantly, they identified a novel Wnt16 interacting components, Ap2b1, that potentiates the activation of JNK and S6 respectively. Their findings shed new insight to the mechanistic function of Wnt16 in preventing articular cartilage breakdown upon injuries. They also provided clinical evidence for the relevance of Wnt16 function in human OA using clinical samples. This work should be of appeal to scientists and researchers working in the field of musculoskeletal biology, and in particular for readers interested in cartilage repair and regeneration.