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Mechanisms and therapeutic implications of cellular senescence in osteoarthritis

Nature Reviews Rheumatology volume 17, pages 47–57 (2021)Cite this article

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Abstract

The development of osteoarthritis (OA) correlates with a rise in the number of senescent cells in joint tissues, and the senescence-associated secretory phenotype (SASP) has been implicated in cartilage degradation and OA. Age-related mitochondrial dysfunction and associated oxidative stress might induce senescence in joint tissue cells. However, senescence is not the only driver of OA, and the mechanisms by which senescent cells contribute to disease progression are not fully understood. Furthermore, it remains uncertain which joint cells and SASP-factors contribute to the OA phenotype. Research in the field has looked at developing therapeutics (namely senolytics and senomorphics) that eliminate or alter senescent cells to stop disease progression and pathogenesis. A better understanding of how senescence contributes to joint dysfunction may enhance the effectiveness of these approaches and provide relief for patients with OA.

Key points

  • Osteoarthritis (OA) pathology overlaps with the senescence of cells in joint tissue and the senescence-associated secretory phenotype.

  • Several hallmarks of senescence are associated with OA, but it is unclear which of these cause disease progression.

  • Ageing, DNA damage and oxidative stress can induce senescence in cells in joint tissue.

  • The complexity of the senescent cellular phenotype necessitates the careful use of biomarkers to identify senescent cells.

  • Targeting senescence for OA therapy is a promising new approach that deserves further investigation.

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Fig. 1: Associations between age-related stress, senescence and OA.
Fig. 2: Model for oxidative stress-induced senescence in joint cells.
Fig. 3: Model for cellular senescence in joint tissue and potential treatments.

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Acknowledgements

The authors’ research work is funded by grants from the National Institute on Aging (RO1 AG044034) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R37 AR049003).

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Authors and Affiliations

  1. Division of Rheumatology, Allergy, and Immunology, Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Philip R. Coryell, Brian O. Diekman & Richard F. Loeser

  2. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA

    Brian O. Diekman

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  1. Philip R. Coryell
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All of the authors researched data for the article, made a substantial contribution to discussion of the content, wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Richard F. Loeser.

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R.F.L. has consulted for Unity Biotechnology (<$1,000). The other authors declare no competing interests.

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Nature Reviews Rheumatology thanks F. Blanco, P. van der Kraan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Coryell, P.R., Diekman, B.O. & Loeser, R.F. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis. Nat Rev Rheumatol 17, 47–57 (2021). https://doi.org/10.1038/s41584-020-00533-7

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