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Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis

Key Points

  • Osteoarthritis (OA) represents the failure of the joint as an organ

  • Synovitis is increasingly recognized as a characteristic of the OA joint, and its presence is associated with increased severity of symptoms, joint dysfunction, and cartilage loss

  • Studies in humans and animal models demonstrate a key role for chronic, low-grade inflammation in the pathogenesis of OA

  • Innate immune pathways, such as the complement and pattern-recognition receptor pathways, are pivotal to the inflammation in OA

  • Clinical trials are needed to determine whether anti-inflammatory therapeutics can prevent or slow disease progression in OA

Abstract

Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. Furthermore, we now appreciate that OA pathogenesis involves not only breakdown of cartilage, but also remodelling of the underlying bone, formation of ectopic bone, hypertrophy of the joint capsule, and inflammation of the synovial lining. That is, OA is a disorder of the joint as a whole, with inflammation driving many pathologic changes. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases: it is chronic, comparatively low-grade, and mediated primarily by the innate immune system. Current treatments for OA only control the symptoms, and none has been FDA-approved for the prevention or slowing of disease progression. However, increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies. Indeed, several anti-inflammatory therapies have shown promise in animal models of OA. Further work is needed to identify effective inhibitors of the low-grade inflammation in OA, and to determine whether therapies that target this inflammation can prevent or slow the development and progression of the disease.

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Figure 1: Radiographic and histologic findings in OA: evidence of inflammation and bone remodelling.
Figure 2: The pathobiology of OA.
Figure 3: The molecular mechanisms of low-grade inflammation in OA.
Figure 4: Targeting low-grade inflammation in OA.

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Acknowledgements

The authors' research is supported by the following awards (to W.H.R.): US Department of Veterans Affairs Merit Review Awards I01BX002345, I01RX000934 and I01RX000588; NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Allergy and Infectious Diseases (NIAID) and the Foundation for the NIH Accelerating Medicines Partnership Program UH2 AR067681; and the Northern California Chapter of the Arthritis Foundation (NCCAF) Center of Excellence.

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W.H.R. and R.M. wrote the article. All authors researched the data for the article, contributed substantially to discussions of its content, and participated in review and/or editing of the manuscript before submission.

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J.S. is an employee of AbbVie. All other authors declare no competing interests.

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Robinson, W., Lepus, C., Wang, Q. et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol 12, 580–592 (2016). https://doi.org/10.1038/nrrheum.2016.136

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