The Wnt signalling pathway is gaining increasing attention in the field of joint pathologies, attributable to its role in the development and homeostasis of the tissues found in the joint, including bone and cartilage. Imbalance in this pathway has been implicated in the development and progression of OA, and interference with the pathway might therefore depict an effective treatment strategy. Though offering multiple opportunities, it is yet to be decided which starting point will bring forth the most promising results. The complexity of the pathway and its interaction with other pathways (such as the TGF-β signalling pathway, which also has a central role in the maintenance of joint homeostasis) means that acting directly on proteins in this signalling cascade entails a high risk of undesired side effects. Therefore, interference with Wnt-induced proteins, such as WISP1, might be an overall more effective and safer therapeutic approach to inhibit the pathological events that take place during OA.