Osteoarthritis Pathophysiology: Therapeutic Target Discovery may Require a Multifaceted Approach

Tonia L Vincent; Tamara Alliston; Mohit Kapoor; Richard F Loeser; Linda Troeberg; Christopher B Little

doi:10.1016/j.cger.2021.11.015

Osteoarthritis Pathophysiology: Therapeutic Target Discovery may Require a Multifaceted Approach

Clin Geriatr Med. 2022 May;38(2):193-219. doi: 10.1016/j.cger.2021.11.015.

Authors

Tonia L Vincent¹, Tamara Alliston², Mohit Kapoor³, Richard F Loeser⁴, Linda Troeberg⁵, Christopher B Little⁶

Affiliations

¹ Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK.
² Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
³ Department of Surgery and Laboratory Medicine and Pathobiology, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, University of Toronto, Toronto, Canada.
⁴ Department of Medicine, Division of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, USA.
⁵ University of East Anglia, Norwich Medical School, Norwich NR4 7UQ, UK.
⁶ Raymond Purves Bone and Joint Research Laboratories, Kolling Institute University of Sydney Faculty of Medicine and Health at Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. Electronic address: christopher.little@sydney.edu.au.

Abstract

Molecular understanding of osteoarthritis (OA) has greatly increased through careful analysis of tissue samples, preclinical models, and large-scale agnostic "-omic" studies. There is broad acceptance that systemic and biomechanical signals affect multiple tissues of the joint, each of which could potentially be targeted to improve patient outcomes. In this review six experts in different aspects of OA pathogenesis provide their independent view on what they believe to be good tractable approaches to OA target discovery. We conclude that molecular discovery has been high but future transformative studies require a multidisciplinary holistic approach to develop therapeutic strategies with high clinical efficacy.

Keywords: Aging; Bone; Cartilage; Fibrosis; Inflammation; Osteoarthritis; Pathophysiology; Treatment targets.

Osteoarthritis Pathophysiology: Therapeutic Target Discovery may Require a Multifaceted Approach

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