title: The Changes in the Expression of NF-KB in a Degenerative Human Intervertebral Disc model.
abstract: We aim at determining the changes in the expression of NF-kB signaling pathway in degenerative intervertebral discs. We collected normal and degenerated intervertebral discs tissues. The normal and degenerated cells were cultivated and their histopathology and immunofluoresence studies were used to observe the position of NF-kB p65 in the cell. We also treated the nucleus pulposus cells with inflammatory factors and inhibitors. Western blot was used to analyze the expression of different proteins. Real time fluorescence-based quantitative PCR was used for observation of NF-kB regulation of change in gene expression. Immunofluorescence showed that in the non-degenerative group the p65 was found in the cytoplasm of the nucleus pulposus cell while in the degenerated cell group the p65 protein was found in the nucleus of the cell. The expression of p65 increased with increase in the degree of degenerative change of the nucleus pulposus cell. RT-PCR showed that the expression of matrix metalloproteinases, aggrecanases and IL-6 was higher in the degenerative group. The amount of aggrecan and type II collagen was significantly decreased in the degenerative group. IL-1β was able to upregulate the activation of NF-kB and the expression of MMP-13 and ADAMTS-4 was also significantly increased. The effect of these proteins can be inhibited by the NF-kB inhibitor, BAY11-7082. The activation of the NK-kB signaling pathway in a degenerative intervertebral disc is gradually increased, regulating the over-expression of matrix-degrading enzymes. It plays an important role in the degradation of extracellular matrix.
authors.affiliation: Department of Orthopedics Surgery, School of Medicine, Shanghai First People's Hospital Affiliated Shanghai Jiao Tong University, 100, Haining Road, Shanghai, 200080, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Orthopedics Surgery, School of Medicine, Shanghai First People's Hospital Affiliated Shanghai Jiao Tong University, 100, Haining Road, Shanghai, 200080, China.|Spine and Joint Surgery, Central Hospital of Tai An, Shandong, China.
authors.forename: Zhanmin
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Orthopedics Surgery, School of Medicine, Shanghai First People's Hospital Affiliated Shanghai Jiao Tong University, 100, Haining Road, Shanghai, 200080, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopedics Surgery, School of Medicine, Shanghai First People's Hospital Affiliated Shanghai Jiao Tong University, 100, Haining Road, Shanghai, 200080, China. tjw609@163.com.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Tian
mesh_terms: D000071121:ADAMTS4 Protein / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D024043:Collagen Type II / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007403:Intervertebral Disc / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D017116:Low Back Pain / Q000188:drug therapy; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009570:Nitriles / Q000737:chemistry; D000070614:Nucleus Pulposus / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013450:Sulfones / Q000737:chemistry; D051996:Transcription Factor RelA / Q000378:metabolism*; D055815:Young Adult
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D024043:Collagen Type II; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D009570:Nitriles; C498143:RELA protein, human; D013450:Sulfones; D051996:Transcription Factor RelA; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human
keywords: Intervertebral disc degeneration; NF-kB; Nucleus pulposus cell; Signaling pathway