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  • Review Article
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Synovial inflammation in osteoarthritis progression

Nature Reviews Rheumatology volume 18, pages 258–275 (2022)Cite this article

Subjects

Abstract

Osteoarthritis (OA) is a progressive degenerative disease resulting in joint deterioration. Synovial inflammation is present in the OA joint and has been associated with radiographic and pain progression. Several OA risk factors, including ageing, obesity, trauma and mechanical loading, play a role in OA pathogenesis, likely by modifying synovial biology. In addition, other factors, such as mitochondrial dysfunction, damage-associated molecular patterns, cytokines, metabolites and crystals in the synovium, activate synovial cells and mediate synovial inflammation. An understanding of the activated pathways that are involved in OA-related synovial inflammation could form the basis for the stratification of patients and the development of novel therapeutics. This Review focuses on the biology of the OA synovium, how the cells residing in or recruited to the synovium interact with each other, how they become activated, how they contribute to OA progression and their interplay with other joint structures.

Key points

  • Imaging studies suggest that synovial inflammation may be present in both early osteoarthritis (OA) and advanced-stage OA and is involved in the development and progression of OA.

  • Synovial cells coordinate the production of molecules that initiate and maintain synovial inflammation and contribute to cartilage damage during OA progression.

  • Diverse stimuli, including bioactive lipids, prostaglandins, tricarboxylic acid cycle intermediates, cytokines and damage-associated molecular patterns, as well as clinical factors such as obesity, ageing, trauma and excessive mechanical loading, regulate the production of pro-inflammatory and anti-inflammatory mediators by synovial cells.

  • There is a need for functional imaging and cellular and molecular studies, together with a more robust histological interpretation at different stages of OA, to better stratify patients with OA and understand the role of synovitis in OA onset and progression.

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Fig. 1: Synovial inflammation and fibrosis in osteoarthritis.
Fig. 2: Osteoarthritis risk factors and synovitis.
Fig. 3: Molecular mediators that contribute to synovial inflammation in osteoarthritis.
Fig. 4: Cellular crosstalk in synovitis and OA progression.

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Acknowledgements

The authors’ work was supported by the US National Institutes of Health (AR073324 to M.G., 5T32AR064194-07 to R.C., NIH Diversity Supplement to A.T., AG070647 and AR078917 to N.E.L., and K01AR077111 and Resource-based Center for the study of the joint microenvironment in rheumatology UCSD (NIH P30AR073761) to E.S.-L.).

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  1. These authors contributed equally: Elsa Sanchez-Lopez, Roxana Coras.

Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of California San Diego, San Diego, CA, USA

    Elsa Sanchez-Lopez

  2. Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California San Diego, San Diego, CA, USA

    Roxana Coras, Alyssa Torres & Monica Guma

  3. Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain

    Roxana Coras & Monica Guma

  4. Division of Rheumatology, Department of Medicine, University of California Davis, Davis, CA, USA

    Nancy E. Lane

  5. San Diego VA Healthcare Service, San Diego, CA, USA

    Monica Guma

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E.S.-L., R.C., N.E.L. and M.G. researched data for the article and contributed substantially to discussion of the content. All authors wrote the article. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Monica Guma.

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Sanchez-Lopez, E., Coras, R., Torres, A. et al. Synovial inflammation in osteoarthritis progression. Nat Rev Rheumatol 18, 258–275 (2022). https://doi.org/10.1038/s41584-022-00749-9

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