Ion channels as therapeutic targets in osteoarthritis

Abstract

Osteoarthritis (OA) is a leading cause of disability worldwide and is characterized by cartilage loss, inflammation, and pain. Despite advances, effective disease-modifying treatments are lacking. Emerging evidence highlights ion channels as key regulators of OA that affect chondrocyte survival, mechanotransduction, inflammation, and nociception. This review discusses ion channel families - including sodium, potassium, TRP, Piezo, acid-sensing, and chloride channels, as well as ligand-gated receptors - and their roles in OA progression. We explore preclinical and clinical advances in ion channel-targeted therapies, such as small-molecule inhibitors, biologics, and gene therapies, as well as repurposing of existing drugs for symptom relief and disease modification. Challenges in selective targeting, pharmacological and drug delivery strategies, and patient stratification are also addressed. Continued research on ion channel biology is essential for developing targeted OA therapies to enable precision medicine via site-specific strategies that minimize systemic side effects.

Keywords: ASIC channels; Piezo channels; TRP channels; ion channels; osteoarthritis; voltage-gated sodium channels.