Jingjing Xie1, Bo Li1, Pingchao Zhang1, Lixin Wang1, Hua Lu1, Xuan Song2. 1. Department of Orthopedic Surgery, Chongming Branched Hospital of Xinhua Hospital Affiliated to Medical School of Shanghai Jiaotong Universtiy, Shanghai 202150, China. 2. Department of Orthopedic Surgery, Chongming Branched Hospital of Xinhua Hospital Affiliated to Medical School of Shanghai Jiaotong Universtiy, Shanghai 202150, China. Electronic address: xuansong2007@163.com.
Abstract
BACKGROUND: Nucleus pulposus (NP) cell senescence correlates with disc degeneration. Previous studies imply that inflammation induces NP cell senescence. Osteogenic protein-1 (OP-1) is helpful for regenerating degenerative disc. OBJECTIVE: To investigate whether OP-1 treatment can protect against the inflammatory cytokine TNF-α-induced NP cell senescence, and its potential mechanism. METHODS: Rat NP cells were cultured in either basic culture medium or basic culture medium with the inflammatory cytokine TNF-α for 3 days. OP-1 was added into the culture medium of TNF-α-treated NP cells to investigate the protective effects of OP-1 against cellular senescence. NP cell senescence was evaluated by some direct and indirect parameters, such as senescence associated β-galactosidase (SA-β-Gal) activity, cell cycle, telomerase activity, expression of senescence markers (p16 and p53), and the matrix homeostatic phenotype. Additionally, intracellular reactive oxygen species (ROS) and the activity of the NF-κB pathway were also analyzed. RESULTS: Compared with the control group, the inflammatory cytokine TNF-α significantly promoted NP cell senescence, reflected by the increase in SA-β-Gal activity, G0/G1 phase fraction and senescence markers (p16 and p53) expression, and the decrease in telomerase activity and matrix macromolecules (aggrecan and collagen II) expression. However, OP-1 suppressed the effects of TNF-α on NP cell senescence. Further analysis showed that OP-1 reduced ROS generation in TNF-α-treated NP cells, as well as the resulting activity of the NF-κB pathway. CONCLUSION: OP-1 can attenuate inflammatory cytokine TNF-α-induced NP cell senescence, and the ROS/ NF-κB pathway may participate in this regulatory process. This study provides that OP-1 may be efficacy in retarding inflammation-exacerbated disc degeneration.
BACKGROUND: Nucleus pulposus (NP) cell senescence correlates with disc degeneration. Previous studies imply that inflammation induces NP cell senescence. Osteogenic protein-1 (OP-1) is helpful for regenerating degenerative disc. OBJECTIVE: To investigate whether OP-1 treatment can protect against the inflammatory cytokine TNF-α-induced NP cell senescence, and its potential mechanism. METHODS:Rat NP cells were cultured in either basic culture medium or basic culture medium with the inflammatory cytokine TNF-α for 3 days. OP-1 was added into the culture medium of TNF-α-treated NP cells to investigate the protective effects of OP-1 against cellular senescence. NP cell senescence was evaluated by some direct and indirect parameters, such as senescence associated β-galactosidase (SA-β-Gal) activity, cell cycle, telomerase activity, expression of senescence markers (p16 and p53), and the matrix homeostatic phenotype. Additionally, intracellular reactive oxygen species (ROS) and the activity of the NF-κB pathway were also analyzed. RESULTS: Compared with the control group, the inflammatory cytokine TNF-α significantly promoted NP cell senescence, reflected by the increase in SA-β-Gal activity, G0/G1 phase fraction and senescence markers (p16 and p53) expression, and the decrease in telomerase activity and matrix macromolecules (aggrecan and collagen II) expression. However, OP-1 suppressed the effects of TNF-α on NP cell senescence. Further analysis showed that OP-1 reduced ROS generation in TNF-α-treated NP cells, as well as the resulting activity of the NF-κB pathway. CONCLUSION: OP-1 can attenuate inflammatory cytokine TNF-α-induced NP cell senescence, and the ROS/ NF-κB pathway may participate in this regulatory process. This study provides that OP-1 may be efficacy in retarding inflammation-exacerbated disc degeneration.
Authors: Siarhei A Dabravolski; Nikita G Nikiforov; Alexander D Zhuravlev; Nikolay A Orekhov; Andrey V Grechko; Alexander N Orekhov Journal: Int J Mol Sci Date: 2022-01-25 Impact factor: 5.923