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Voltage-Dependent Calcium Channels in Chondrocytes: Roles in Health and Disease

  • Osteoarthritis (MB Goldring, Section Editor)
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Abstract

Chondrocytes, the single cell type in adult articular cartilage, have conventionally been considered to be non-excitable cells. However, recent evidence suggests that their resting membrane potential (RMP) is less negative than that of excitable cells, and they are fully equipped with channels that control ion, water and osmolyte movement across the chondrocyte membrane. Amongst calcium-specific ion channels, members of the voltage-dependent calcium channel (VDCC) family are expressed in chondrocytes where they are functionally active. L-type VDCC inhibitors such as nifedipine and verapamil have contributed to our understanding of the roles of these ion channels in chondrogenesis, chondrocyte signalling and mechanotransduction. In this narrative review, we discuss published data indicating that VDCC function is vital for chondrocyte health, especially in regulating proliferation and maturation. We also highlight the fact that activation of VDCC function appears to accompany various inflammatory aspects of osteoarthritis (OA) and, based on in vitro data, the application of nifedipine and/or verapamil may be a promising approach for ameliorating OA severity. However, very few studies on clinical outcomes are available regarding the influence of calcium antagonists, which are used primarily for treating cardiovascular conditions in OA patients. This review is intended to stimulate further research on the chondrocyte ‘channelome’, contribute to the development of novel therapeutic strategies and facilitate the retargeting and repositioning of existing pharmacological agents currently used for other comorbidities for the treatment of OA.

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Acknowledgments

Csaba Matta is supported by the European Commission through a Marie Skłodowska-Curie Intra-European Fellowship for career development (project number: 625746; acronym: CHONDRION; FP7-PEOPLE-2013-IEF). Ali Mobasheri is the co-ordinator of the D-BOARD Consortium funded by European Commission Framework 7 programme (EU FP7; HEALTH.2012.2.4.5-2, project number 305815, Novel Diagnostics and Biomarkers for Early Identification of Chronic Inflammatory Joint Diseases). Ali Mobasheri is also a member of the Arthritis Research UK Centre for Sport, Exercise, and Osteoarthritis, funded by Arthritis Research UK (Grant Reference: 20194). Csaba Matta and Róza Zákány are supported by a research and development grant from the Hungarian Government (project number: GOP-1.1.1-11-2012-0197). The authors are especially indebted to Dr Sita Bierma-Zeinstra, Professor of osteoarthritis and related disorders at Erasmus Medical Centre in Rotterdam, The Netherlands, for the critical comments on the clinical aspects of this paper.

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Conflict of Interest

Csaba Matta, Róza Zákány and Ali Mobasheri declare no conflicts of interest. The authors wrote this paper within the scope of their academic and affiliated research positions. The authors do not have any commercial relationships that could be construed as biased or inappropriate.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. The D-BOARD European Consortium for Biomarker Discovery, Department of Veterinary Preclinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK

    Csaba Matta & Ali Mobasheri

  2. Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4032, Hungary

    Csaba Matta & Róza Zákány

  3. Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen’s Medical Centre, Nottingham, NG7 2UH, UK

    Ali Mobasheri

  4. Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), King AbdulAziz University, Jeddah, 21589, Kingdom of Saudi Arabia

    Ali Mobasheri

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  1. Csaba Matta
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Correspondence to Csaba Matta.

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Matta, C., Zákány, R. & Mobasheri, A. Voltage-Dependent Calcium Channels in Chondrocytes: Roles in Health and Disease. Curr Rheumatol Rep 17, 43 (2015). https://doi.org/10.1007/s11926-015-0521-4

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