Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Oct 27;28(1):88.
doi: 10.1186/s11658-023-00501-5.

Cellular senescence in skeletal disease: mechanisms and treatment

Xu He #  1 , Wei Hu #  1 , Yuanshu Zhang #  2 , Mimi Chen  3 , Yicheng Ding  4 , Huilin Yang  1 , Fan He  5 , Qiaoli Gu  6 , Qin Shi  7   8
Affiliations
Review

Cellular senescence in skeletal disease: mechanisms and treatment

Xu He et al. Cell Mol Biol Lett. .

Abstract

The musculoskeletal system supports the movement of the entire body and provides blood production while acting as an endocrine organ. With aging, the balance of bone homeostasis is disrupted, leading to bone loss and degenerative diseases, such as osteoporosis, osteoarthritis, and intervertebral disc degeneration. Skeletal diseases have a profound impact on the motor and cognitive abilities of the elderly, thus creating a major challenge for both global health and the economy. Cellular senescence is caused by various genotoxic stressors and results in permanent cell cycle arrest, which is considered to be the underlying mechanism of aging. During aging, senescent cells (SnCs) tend to aggregate in the bone and trigger chronic inflammation by releasing senescence-associated secretory phenotypic factors. Multiple signalling pathways are involved in regulating cellular senescence in bone and bone marrow microenvironments. Targeted SnCs alleviate age-related degenerative diseases. However, the association between senescence and age-related diseases remains unclear. This review summarises the fundamental role of senescence in age-related skeletal diseases, highlights the signalling pathways that mediate senescence, and discusses potential therapeutic strategies for targeting SnCs.

Keywords: Age-related orthopaedic diseases; Bone marrow; Cellular senescence; Chronic inflammation; Signalling pathways.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no conflicts of interest exist.

Figures

Fig. 1
Fig. 1
Strategies targeting cellular senescence in osteoporosis. Senescent MSCs (red arrows) can inhibit the osteogenic differentiation and promote adipogenic differentiation of physiologic MSCs. Senescent macrophages (red arrows) can enhance osteoclast activity. Senescent osteocytes secrete high levels of RANKL to promote osteoclast activity leading to increased bone loss. A common feature of SnCs is the development of SASP. "Senolytics" and "senomophics" (yellow arrows) are necessary to counteract the adverse effects of SnCs by killing SnCs and inhibiting SASP secreted by senescent cells, respectively
Fig. 2
Fig. 2
Strategies targeting cellular senescence in osteoarthritis. In OA, various cells can secrete SASP components. When SnCs persist, molecules secreted by SnCs and immune cells can cause chronic inflammation, eventually leading to OA
See this image and copyright information in PMC

References

    1. Safiri S, Kolahi AA, Smith E, Hill C, Bettampadi D, Mansournia MA, et al. Global, regional and national burden of osteoarthritis 1990–2017: a systematic analysis of the Global Burden of Disease Study 2017. Ann Rheum Dis. 2020;79(6):819–828. doi: 10.1136/annrheumdis-2019-216515. - DOI - PubMed
    1. Aibar-Almazán A, Voltes-Martínez A, Castellote-Caballero Y, Afanador-Restrepo DF, Carcelén-Fraile MDC, López-Ruiz E. Current status of the diagnosis and management of osteoporosis. Int J Mol Sci. 2022;23(16). - PMC - PubMed
    1. Jang S, Lee K, Ju JH. Recent updates of diagnosis, pathophysiology, and treatment on osteoarthritis of the knee. Int J Mol Sci. 2021;22(5). - PMC - PubMed
    1. Melzer D, Pilling LC, Ferrucci L. The genetics of human ageing. Nat Rev Genet. 2020;21(2):88–101. doi: 10.1038/s41576-019-0183-6. - DOI - PMC - PubMed
    1. Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W, Mitchell JR, et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell. 2014;31(6):722–733. doi: 10.1016/j.devcel.2014.11.012. - DOI - PMC - PubMed