Ion channels in osteoarthritis: emerging roles and potential targets
Renpeng Zhou1, Wenyu Fu1, Dmytro Vasylyev2
1Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA.
Abstract:
Osteoarthritis (OA) is a highly prevalent joint disease that causes substantial disability, yet effective approaches to disease prevention or to the delay of OA progression are lacking. Emerging evidence has pinpointed ion channels as pivotal mediators in OA pathogenesis and as promising targets for disease-modifying treatments. Preclinical studies have assessed the potential of a variety of ion channel modulators to modify disease pathways involved in cartilage degeneration, synovial inflammation, bone hyperplasia and pain, and to provide symptomatic relief in models of OA. Some of these modulators are currently being evaluated in clinical trials. This review explores the structures and functions of ion channels, including transient receptor potential channels, Piezo channels, voltage-gated sodium channels, voltage-dependent calcium channels, potassium channels, acid-sensing ion channels, chloride channels and the ATP-dependent P2XR channels in the osteoarthritic joint. The discussion spans channel-targeting drug discovery and potential clinical applications, emphasizing opportunities for further research, and underscoring the growing clinical impact of ion channel biology in OA.
Insights
Ion channels are key players in osteoarthritis (OA) development and progression. Targeting these channels offers a promising new strategy for developing effective OA treatments and therapies.
Area of Science:
- Biomedical Science
- Molecular Biology
- Pharmacology
Background:
- Osteoarthritis (OA) is a widespread joint disease causing significant disability.
- Current OA treatments lack disease-modifying capabilities for prevention or progression delay.
Purpose of the Study:
- To review the role of ion channels in osteoarthritis pathogenesis.
- To explore ion channel modulators as potential therapeutic targets for OA.
- To discuss the clinical applications and future research directions for ion channel-based OA treatments.
Main Methods:
- Literature review of preclinical and clinical studies on ion channels in OA.
- Analysis of ion channel structures and functions relevant to OA.
- Examination of drug discovery efforts targeting ion channels in OA.
Main Results:
- Ion channels (TRP, Piezo, NaV, CaV, K+, ASIC, Cl-, P2XR) are implicated in OA pathology.
- Ion channel modulators show potential in preclinical OA models for cartilage, bone, inflammation, and pain.
- Several ion channel modulators are under clinical investigation for OA treatment.
Conclusions:
- Ion channels are critical mediators in osteoarthritis.
- Targeting ion channels represents a promising avenue for disease-modifying OA therapies.
- Further research into ion channel biology will advance OA treatment strategies.
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