Mechanisms and therapeutic implications of cellular senescence in osteoarthritis

By Philip R. Coryell, B. Diekman, Richard F. Loeser. Nature Reviews Rheumatology, 2020

648 citations recorded by the source corpus.

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. The development of osteoarthritis (OA) correlates with an increase in the number of senescent cells in joint tissues and the senescence-associated secretory phenotype is implicated in cartilage degradation and OA. Eliminating or altering senescent cells with senolytics or senomorphics could stop OA progression and pathogenesis. 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.

Subfields: Immunology, Physiology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/52e6d0849cae82436d87dcb8bdf02c5aaba69711

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Citations in the corpus

• Osteoarthritis: pathogenic signaling pathways and therapeutic targets (2023, background): “Several potential pathological mechanisms of how aging contributes to OA have been proposed recently.(41,42) The cellular senescence-associated secretory phenotype (SASP) has been detected in the degradative articular cartilage and synovial joint tissue of developing OA.”