Intervertebral disc degeneration(IDD)is featured as enhanced catabolism of extracellular matrix(ECM)in the nucleus pulposus(NP),in which tumor necrosis factor-alpha(TNF-α)-related cell senescence is involved.Chro-mobox homolog protein 4(CBX4)exhibits anti-inflammatory effects and shows promising therapeutic potential.Thus,in the present study,we explore the role of CBX4 in IDD.Immunohistochemistry staining reveals that CBX4 expression is decreased in severe degenerative NP tissues compared to mild degenerative tissues,and real-time PCR and western blot analysis results show that CBX4 expression is downregulated under TNF-α stimulation in NP cells.siRNA and adenoviruses are used to knockdown or overexpress CBX4,respectively.The results demonstrate that CBX4 knockdown augments the catabolism of ECM in human NP cells,while CBX4 overexpression in rat NP cells restores the ECM degradation induced by TNF-α,as illustrated by immunofluorescence and western blot analysis.In addition,transcriptome sequencing results reveal the regulatory effect of CBX4 on the cell cycle,and further western blot analysis and senescence-associated β-galactosidase staining assay indicate that CBX4 over-expression alleviates cell senescence in the presence of TNF-α.Moreover,the phosphorylation of p65,which indicates the activation of NF-κB signaling,is measured by western blot analysis and immunofluorescence assay,and the results reveal that CBX4 overexpression reduces the TNF-α-induced increase in the p-p65/p65 ratio.In addition,the effect of CBX4 overexpression in NP cells is suppressed by NF-κB agonist.In summary,our results indicate that CBX4 overexpression can suppress TNF-α-induced matrix catabolism and cell senescence in the NP by inhibiting NF-κB activation.This study may provide new approaches for preventing and treating IDD.

Yangyang Zhang;Shuangxing Li;Junmin Hong;Jiansen Yan;Zhengqi Huang;Jiajun Wu;Zhihuai Deng;Tianyu Qin;Kang Xu;Wei Ye

Department of Spine Surgery,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou 510289,China;Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Medical Research Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510289,China;Department of Orthopedics,the Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen 518107,China;Department of Orthopedics,the Eighth Affiliated Hospital of Sun Yat-sen University,Shenzhen 518033,China

生物化学与生物物理学报（英文版）

[1]Yangyang Zhang;Shuangxing Li;Junmin Hong;Jiansen Yan;Zhengqi Huang;Jiajun Wu;Zhihuai Deng;Tianyu Qin;Kang Xu;Wei Ye-.Chromobox homolog 4 overexpression inhibits TNF-α-induced matrix catabolism and senescence by suppressing activation of NF-κB signaling pathway in nucleus pulposus cells)[J].生物化学与生物物理学报（英文版）,2022(07):1021-1029

Chromobox,Chro,mobox,adenoviruses

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