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WNT Signalling in Osteoarthritis and Its Pharmacological Targeting

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Pharmacology of the WNT Signaling System

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 269))

Abstract

Osteoarthritis (OA) is a highly disabling musculoskeletal condition affecting millions of people worldwide. OA is characterised by progressive destruction and irreversible morphological changes of joint tissues and architecture. At molecular level, de-regulation of several pathways contributes to the disruption of tissue homeostasis in the joint. Overactivation of the WNT/β-catenin signalling pathway has been associated with degenerative processes in OA. However, the multiple layers of complexity in the modulation of the signalling and the still insufficient knowledge of the specific molecular drivers of pathogenetic mechanisms have made difficult the pharmacological targeting of this pathway for therapeutic purposes. This review aims to provide an overview of the WNT/β-catenin signalling in OA with a particular focus on its role in the articular cartilage. Pathway components whose targeting showed therapeutic potential will be highlighted and described. A specific section will be dedicated to Lorecivivint, the first inhibitor of the β-catenin-dependent pathway currently in phase III clinical trial as OA-modifying agent.

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Acknowledgement

Funding: This work was supported by the Medical Research Council MR/S008608/1.

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  1. Department of Veterinary Pre-Clinical Sciences, School of Veterinary Medicine, University of Surrey, Guildford, UK

    Anna De Palma & Giovanna Nalesso

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  1. Anna De Palma
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  2. Giovanna Nalesso
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Correspondence to Giovanna Nalesso .

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  1. Department of Physiology & Pharmacology Section for Receptor Biology & Signaling, Karolinska Institutet Biomedicum 6D, Stockholm, Sweden

    Gunnar Schulte

  2. Department of Physiology & Pharmacology Section for Receptor Biology & Signaling, Karolinska Institutet Biomedicum 6D, Stockholm, Sweden

    Pawel Kozielewicz

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De Palma, A., Nalesso, G. (2021). WNT Signalling in Osteoarthritis and Its Pharmacological Targeting. In: Schulte, G., Kozielewicz, P. (eds) Pharmacology of the WNT Signaling System. Handbook of Experimental Pharmacology, vol 269. Springer, Cham. https://doi.org/10.1007/164_2021_525

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