Urolithin a alleviates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells through SIRT1/PGC-1α pathway

• Published in: World journal of stem cells Vol. 13; no. 12; pp. 1928 - 1946
• Main Authors: Shi, Peng-Zhi, Wang, Jun-Wu, Wang, Ping-Chuan, Han, Bo, Lu, Xu-Hua, Ren, Yong-Xin, Feng, Xin-Min, Cheng, Xiao-Fei, Zhang, Liang
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 26.12.2021
• Subjects: Basic Study; Oxidative stress; The silent information regulator of transcription 1/PPAR gamma coactivator-1α pathway; Senescence; Urolithin A; Mitochondrial function; Nucleus pulposus-derived Mesenchymal stem cells
• ISSN: 1948-0210; 1948-0210
• DOI: 10.4252/wjsc.v13.i12.1928

In degenerative intervertebral disc (IVD), an unfavorable IVD environment leads to increased senescence of nucleus pulposus (NP)-derived mesenchymal stem cells (NPMSCs) and the inability to complete the differentiation from NPMSCs to NP cells, leading to further aggravation of IVD degeneration (IDD). Urolithin A (UA) has been proven to have obvious effects in delaying cell senescence and resisting oxidative stress. To explore whether UA can alleviate NPMSCs senescence and to elucidate the underlying mechanism. , we harvested NPMSCs from rat tails, and divided NPMSCs into four groups: the control group, H O group, H O + UA group, and H O + UA + SR-18292 group. Senescence-associated β-Galactosidase (SA-β-Gal) activity, cell cycle, cell proliferation ability, and the expression of senescence-related and silent information regulator of transcription 1/PPAR gamma coactivator-1α (SIRT1/ PGC-1α) pathway-related proteins and mRNA were used to evaluate the protective effects of UA. , an animal model of IDD was constructed, and X-rays, magnetic resonance imaging, and histological analysis were used to assess whether UA could alleviate IDD . We found that H O can cause NPMSCs senescence changes, such as cell cycle arrest, reduced cell proliferation ability, increased SA-β-Gal activity, and increased expression of senescence-related proteins and mRNA. After UA pretreatment, the abovementioned senescence indicators were significantly alleviated. To further demonstrate the mechanism of UA, we evaluated the mitochondrial membrane potential and the SIRT1/PGC-1α pathway that regulates mitochondrial function. UA protected mitochondrial function and delayed NPMSCs senescence by activating the SIRT1/PGC-1α pathway. , we found that UA treatment alleviated an animal model of IDD by assessing the disc height index, Pfirrmann grade and the histological score. In summary, UA could activate the SIRT1/PGC-1α signaling pathway to protect mitochondrial function and alleviate cell senescence and IDD and .