Abstract
Aging is a major risk factor for degenerative joint diseases, such as osteoarthritis (OA). Previous studies have confirmed the link between senescent mesenchymal stem cells (MSCs) and OA. Cartilage-derived stem/progenitor cells (CSPCs) with MSCs properties have been extracted from a variety of species. We inferred that the senescence of CSPCs may promote the development of osteoarthritis. However, the cellular and molecular mechanisms of CSPCs senescence remains unknown. In this study, we investigated the role of JAK-STAT signaling pathway in a replicative senescence model of CSPCs. We showed that the late CSPCs (> 15th passage) exhibited distinct senescent phenotypes, including increased proportion of β-gal positive senescent cells and F-actin content, as well as cell cycle arrest. In late CSPCs, the activity of JAK-STAT signaling pathway was significantly increased. Activation of JAK-STAT signaling pathway promoted cell senescence in early CSPCs (< 6th passage). Conversely, pharmacological inhibition or genetic knockdown of JAK-STAT signaling pathway attenuated cell senescence in late CSPCs. In conclusion, our results demonstrated the critical role of JAK-STAT signaling pathway in CSPCs senescence.
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This work was supported by Clinical Center Construction Project of Nantong (HS2019004), A Project of Nantong Science and Technology Program (JC2020015); The Research Innovation Program for College Graduates of Jiangsu Province (KYCX20-2800).
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Ji, T., Chen, M., Sun, W. et al. JAK-STAT signaling mediates the senescence of cartilage-derived stem/progenitor cells. J Mol Histol 53, 635–643 (2022). https://doi.org/10.1007/s10735-022-10086-6
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DOI: https://doi.org/10.1007/s10735-022-10086-6