Emerging therapeutic targets for osteoarthritis
Ermina Hadzic1,2, Frank Beier1,2
1Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
Introduction:
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.
Areas Covered:
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.
Expert Opinion:
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.
Insights
This review explores emerging osteoarthritis therapeutic targets in animal and early clinical studies, including autophagy, senescence, and growth factor pathways. Challenges remain in translating these findings to effective treatments due to disease complexity.
Area of Science:
- Orthopedics and Regenerative Medicine
- Pharmacology and Drug Discovery
Background:
- Osteoarthritis (OA) is a complex joint disease lacking disease-modifying drugs.
- Animal models are crucial for understanding OA pathology and identifying therapeutic targets.
Approach:
- A literature search (2017-2021) identified OA targets including autophagy, senescence, TGF-beta, EGFR, Wnt/β-catenin, and inflammation.
- Specific pathways examined include PI3/AKT/mTOR, epidermal growth factor receptor, Toll-like receptors, and inflammatory interleukins.
Key Points:
- The field of OA therapeutic targets has expanded significantly, revealing new targets and improved drug delivery methods.
- Understanding of previously identified targets has deepened.
- Viral vectors offer potential for enhanced drug delivery.
Conclusions:
- Translating preclinical findings into clinical benefits for OA remains challenging.
- Disease heterogeneity, lack of early diagnostics, and mismatched animal models contribute to this translational gap.
- The complex roles of many potential therapeutic targets require further investigation.
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