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The Role of Osteoprotegerin in Vascular Calcification and Bone Metabolism: The Basis for Developing New Therapeutics

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Abstract

Osteoporosis (OP) and cardiovascular diseases (CVD) are both important causes of mortality and morbidity in aging patients. There are common mechanisms underlying the regulation of bone remodeling and the development of smooth muscle calcification; a temporal relationship exists between osteoporosis and the imbalance of mineral metabolism in the vessels. Vascular calcification appears regulated by mechanisms that include both inductive and inhibitory processes. Multiple factors are implicated in both bone and vascular metabolism. Among these factors, the superfamily of tumor necrosis factor (TNF) receptors including osteoprotegerin (OPG) and its ligands has been established. OPG is a soluble decoy receptor for receptor activator of nuclear factor-kB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). OPG binds to RANKL and TRAIL, and inhibits the association with their receptors, which have been labeled as the receptor activator of NF-kB (RANK). Sustained release of OPG from vascular endothelial cells (ECs) has been demonstrated in response to inflammatory proteins and cytokines, suggesting that OPG/RANKL/RANK system plays a modulatory role in vascular injury and inflammation. For the development of potential therapeutic strategies targeting vascular calcification, critical consideration of the implications for bone metabolism must be taken into account to prevent potentially detrimental effects to bone metabolism.

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Acknowledgements

The authors wish to thank Philip Bastable for English assistance.

Funding

This work was supported by grants from French Ministry of Research, INSERM (Institut national de la santé et de la recherche médicale) and from the Regional Council of Burgundy (Conseil Régional de Bourgogne), FEDER, and Association de Cardiologie de Bourgogne. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Authors and Affiliations

  1. Equipe d’Accueil (EA 7460): Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Université de Bourgogne – Franche Comté, Faculté des Sciences de Santé, 7 Bd Jeanne d’Arc, 21000, Dijon, France

    Luc Rochette, Alexandre Meloux, Eve Rigal, Marianne Zeller, Yves Cottin & Catherine Vergely

  2. Institut de formation en Biotechnologie et Ingénierie Biomédicale (IFR2B), Université Mohammed VI Polytechnique, 43 150, Ben-Guerir, Morocco

    Gabriel Malka

  3. Service de Cardiologie-CHU-Dijon, Dijon, France

    Yves Cottin

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  1. Luc Rochette
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  2. Alexandre Meloux
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  4. Marianne Zeller
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Correspondence to Luc Rochette.

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Luc Rochette, Alexandre Meloux, Eve Rigal, Marianne Zeller, Gabriel Malka, Yves Cottin, and Catherine Vergely declare that they did not receive funding from any sources and had no conflicts of interest.

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Rochette, L., Meloux, A., Rigal, E. et al. The Role of Osteoprotegerin in Vascular Calcification and Bone Metabolism: The Basis for Developing New Therapeutics. Calcif Tissue Int 105, 239–251 (2019). https://doi.org/10.1007/s00223-019-00573-6

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