Emerging therapeutic targets for osteoarthritis

Osteoarthritis is a heterogeneous joint disorder that lacks a clinically meaningful disease modifying drug. Animal models have been beneficial in understanding basic joint pathology and providing rationale for future clinical trials on identified targets. This review aims to discuss promising therapeutic targets of osteoarthritis that are currently in animal studies or early clinical trials.PubMed was searched for articles published between 2017 and 2021 with the following terms: (osteoarthritis AND autophagy) OR (osteoarthritis AND senescence) OR (osteoarthritis AND TGFbeta) OR (osteoarthritis AND EGFR) OR (osteoarthritis AND Wnt/β-catenin) OR (osteoarthritis AND inflammation). Specific targets include the PI3/AKT/mTOR pathway, epidermal growth factor receptor, Toll-like receptors, and inflammatory interleukins, among others.In reviewing these targets, it is clear that the field of therapeutic targets for osteoarthritis has grown tremendously. We have gained a better understanding of previously identified targets, identified new targets, and have the opportunity to explore enhanced drug delivery via viral vectors. Regardless, translation to clinical benefits is still lacking in most cases. We propose that this may be due to the heterogeneous nature of the disease, lack of early diagnostic markers, mismatched preclinical animal models and clinical populations, and the complex role of many targets of interest.