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Inflammaging and Osteoarthritis

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Abstract

Osteoarthritis is a highly prevalent disease particularly in subjects over 65 years of age worldwide. While in the past it was considered a mere consequence of cartilage degradation leading to anatomical and functional joint impairment, in recent decades, there has been a more dynamic view with the synovium, the cartilage, and the subchondral bone producing inflammatory mediators which ultimately lead to cartilage damage. Inflammaging is defined as a chronic, sterile, low-grade inflammation state driven by endogenous signals in the absence of infections, occurring with aging. This chronic status is linked to the production of reactive oxygen species and molecules involved in the development of age-related disease such as cancer, diabetes, and cardiovascular and neurodegenerative diseases. Inflammaging contributes to osteoarthritis development where both the innate and the adaptive immune response are involved. Elevated systemic and local inflammatory cytokines and senescent molecules promote cartilage degradation, and antigens derived from damaged joints further trigger inflammation through inflammasome activation. B and T lymphocyte populations also change with inflammaging and OA, with reduced regulatory functions, thus implicating self-reactivity as an additional mechanism of joint damage. The discovery of the underlying pathogenic pathways may help to identify potential therapeutic targets for the management or the prevention of osteoarthritis. We will provide a comprehensive evaluation of the current literature on the role of inflammaging in osteoarthritis and discuss the emerging therapeutic strategies.

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Funding

FM, AS, and CS were funded by the Italian Ministry of Health (Ricerca Corrente and grant RF-2016–02364842).

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Authors and Affiliations

  1. Division of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089, Rozzano, Milan, Italy

    Francesca Motta, Elisa Barone, Antonio Sica & Carlo Selmi

  2. Department of Biomedical Sciences, Humanitas University, via Rita Levi Montalcini, 20090, Pieve Emanuele, Milan, Italy

    Francesca Motta, Elisa Barone & Carlo Selmi

  3. Department of Pharmaceutical Sciences, Università del Piemonte Orientale “Amedeo Avogadro”, Largo Donegani 2, 28100, Novara, Italy

    Antonio Sica

Authors
  1. Francesca Motta
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  2. Elisa Barone
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  3. Antonio Sica
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  4. Carlo Selmi
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Contributions

Both FM and CS conceived the idea for the paper. FM and EB performed the literature search and drafted the manuscript. CS and AS provided helpful suggestions in the preparation of this manuscript, and all the authors reviewed and approved the final version of the paper.

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Correspondence to Carlo Selmi.

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Motta, F., Barone, E., Sica, A. et al. Inflammaging and Osteoarthritis. Clinic Rev Allerg Immunol 64, 222–238 (2023). https://doi.org/10.1007/s12016-022-08941-1

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