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Musculoskeletal imaging of senescence

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Abstract

Senescent cells play a vital role in the pathogenesis of musculoskeletal (MSK) diseases, such as chronic inflammatory joint disorders, rheumatoid arthritis (RA), and osteoarthritis (OA). Cellular senescence in articular joints represents a response of local cells to persistent stress that leads to cell-cycle arrest and enhanced production of inflammatory cytokines, which in turn perpetuates joint damage and leads to significant morbidities in afflicted patients. It has been recently discovered that clearance of senescent cells by novel “senolytic” therapies can attenuate the chronic inflammatory microenvironment of RA and OA, preventing further disease progression and supporting healing processes. To identify patients who might benefit from these new senolytic therapies and monitor therapy response, there is an unmet need to identify and map senescent cells in articular joints and related musculoskeletal tissues. To fill this gap, new imaging biomarkers are being developed to detect and characterize senescent cells in human joints and musculoskeletal tissues. This review article will provide an overview of these efforts. New imaging biomarkers for senescence cells are expected to significantly improve the specificity of state-of-the-art imaging technologies for diagnosing musculoskeletal disorders.

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Funding

This work was funded by a grant from the National Institutes of Health and the Common Fund’s Cellular Senescence Network (SenNet) Program, grant number UG3/UH3CA268112.

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Authors and Affiliations

  1. Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, USA

    Heike E. Daldrup-Link, Vidyani Suryadevara, Yasemin Tanyildizi & Kerem Nernekli

  2. Department of Chemistry, Northwestern University, Evanston, USA

    Jian-Hong Tang & Thomas J. Meade

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  1. Heike E. Daldrup-Link
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  2. Vidyani Suryadevara
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Correspondence to Heike E. Daldrup-Link.

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Key Points

- Senescent cells are key mediators of many musculoskeletal (MSK) diseases, such as osteoarthritis, rheumatoid arthritis and osteoporosis, among others.

- The development and clinical approval of new senolytic therapies create an urgent need for biomarkers that can detect senescent cells with clinical imaging tools.

- New beta-gal-sensitive MRI and PET imaging agents can detect senescent cells in arthritic joints and are currently being translated to the clinic.

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Daldrup-Link, H.E., Suryadevara, V., Tanyildizi, Y. et al. Musculoskeletal imaging of senescence. Skeletal Radiol (2024). https://doi.org/10.1007/s00256-024-04585-8

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