| Home | Magazines | Editorial Board | Instruction | Subscribe Guide | Archive | Advertising | Template | Guestbook | Help |
| PENG Xin,WANG Zhiqiang,ZHANG Tong.Research on the role and mechanism of mitochondrial targeting peptide SS-31 in inflammation-induced senescence and pyroptosis of nucleus pulposus cells[J].Chinese Journal of Spine and Spinal Cord,2025,(4):399-407. |
| Research on the role and mechanism of mitochondrial targeting peptide SS-31 in inflammation-induced senescence and pyroptosis of nucleus pulposus cells |
| Received:August 22, 2024 Revised:January 11, 2025 |
| English Keywords:SS-31 Nucleus pulposus cells Inflammation Senescence Pyroptosis |
| Fund:国家自然科学基金面上项目（82172438、82372470、81871810） |
|
| Hits: 218 |
| Download times: 0 |
| English Abstract: |
| 【Abstract】 Objectives: To investigate the effect and mechanism of mitochondrial targeting peptide SS-31 on senescence and pyroptosis of nucleus pulposus(NP) cells induced by inflammation. Methods: NP cells were isolated and cultured in vitro from 6-week-old male SD rats, and were divided into control group, lipopolysaccharide(LPS) group, and LPS+SS-31 group; And the control group of cells received no treatment, LPS group of cells were treated with 100μg/mL LPS for 24h, and LPS+SS-31 group of cells were pre-treated with SS-31 30min before LPS intervention. The levels of cellular senescence and pyroptosis were assessed in each group using β-galactosidase(SA-β-Gal) staining and western blot(WB) assay; Transmission electron microscopy and oxygen consumption rate(OCR) assay were used to analyze the mitochondrial function of NP cells in each group; The expressions of phosphorylated nuclear factor-κB-p65(p-NF-κB-p65), cyclic GMP-AMP synthase(cGAS), and interferon stimulating gene(STING) in each group were detected by WB and immunofluorescence; Hematoxylin-eosin(HE) staining, immunohistochemistry(IHC) staining and WB assay were performed to analyze the effects of in vivo injection of SS-31 on intervertebral disc degeneration, senescence, and pyroptosis. Results: The positive SA-β-Gal staining of NP cells, expression of senescence marker proteins(p53, p21), and pyroptosis-related molecules(NLRP3, Caspase-1 p20) were significantly lower in the LPS+SS-31 group compared with the LPS group(P<0.05); Transmission electron microscopy(TEM) showed that the mitochondrial swelling of NP cells was round, the matrix was translucent, and the interstitial lumen of the mitochondrial cristae was dilated in the LPS group, while the mitochondrial swelling was subsided, and the morphology of mitochondria tended to be normalized in the LPS+SS-31 group. Meanwhile, the maximum respiration level of NP cells was significantly enhanced in the LPS+SS-31 group compared with the LPS group(P<0.05). The results of WB and immunofluorescence showed that LPS significantly up-regulated the expression of p-NF-κB-p65, cGAS, and STING(P<0.05), while SS-31 pretreatment significantly inhibited the expression of p-NF-κB-p65, cGAS and STING in NP cells induced by LPS(P<0.05). Finally, in vivo experiments confirmed that local injection of SS-31 reduced the senescence and pyroptosis of NP cells, and alleviated the degeneration of intervertebral disc induced by annulus fibropuncture. Conclusions: SS-31 alleviates inflammation-induced senescence and pyroptosis of NP cells, which is related to the inhibition of NF-κB signaling pathway and cGAS/STING signaling pathway. |
| View Full Text View/Add Comment Download reader |
| Close |
|
|
|
|
|