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Biologic response of degenerative living human nucleus pulposus cells to treatment with cytokines

Authors
 Sang Hyun Kim  ;  Sung Uk Kuh  ;  Keung Nyun Kim  ;  Jeong Yoon Park  ;  Ki Hong Cho  ;  Dong Kyu Chin  ;  Keun Su Kim  ;  Yong Eun Cho 
Citation
 YONSEI MEDICAL JOURNAL, Vol.56(1) : 277-286, 2015 
Journal Title
YONSEI MEDICAL JOURNAL
ISSN
 0513-5796 
Issue Date
2015
MeSH
Adult ; Aggrecans/genetics ; Aggrecans/metabolism ; Alkaline Phosphatase/genetics ; Alkaline Phosphatase/metabolism ; Biological Products/pharmacology ; Biological Products/therapeutic use* ; Bone Morphogenetic Protein 2/pharmacology ; Bone Morphogenetic Protein 2/therapeutic use ; Collagen Type I/genetics ; Collagen Type I/metabolism ; Collagen Type II/genetics ; Collagen Type II/metabolism ; Cytokines/pharmacology* ; Cytokines/therapeutic use* ; Female ; Fluorescent Antibody Technique ; Gene Expression Regulation/drug effects ; Humans ; Interleukin-1/pharmacology ; Interleukin-1/therapeutic use ; Intervertebral Disc/drug effects* ; Intervertebral Disc/pathology* ; Intervertebral Disc Degeneration/drug therapy* ; Intervertebral Disc Degeneration/genetics ; Intervertebral Disc Degeneration/pathology* ; Male ; Middle Aged ; Osteocalcin/genetics ; Osteocalcin/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use ; SOX9 Transcription Factor/genetics ; SOX9 Transcription Factor/metabolism ; Transforming Growth Factor beta/pharmacology ; Transforming Growth Factor beta/therapeutic use ; Tumor Necrosis Factor-alpha/pharmacology
Keywords
Cytokine ; IL-1β ; TGF-β ; TNF-α ; disc degeneration ; rhBMP-2
Abstract
PURPOSE: To investigate the molecular responses of various genes and proteins related to disc degeneration upon treatment with cytokines that affect disc-cell proliferation and phenotype in living human intervertebral discs (IVDs). Responsiveness to these cytokines according to the degree of disc degeneration was also evaluated.
MATERIALS AND METHODS: The disc specimens were classified into two groups: group 1 (6 patients) showed mild degeneration of IVDs and group 2 (6 patients) exhibited severe degeneration of IVDs. Gene expression was analyzed after treatment with four cytokines: recombinant human bone morphogenic protein (rhBMP-2), transforming growth factor-β (TGF-β), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Molecular responses were assessed after exposure of cells from the IVD specimens to these cytokines via real-time polymerase chain reaction and immunofluorescence staining.
RESULTS: mRNA gene expression was significantly greater for aggrecan, type I collagen, type II collagen, alkaline phosphatase, osteocalcin, and Sox9 in group 1 than mRNA gene expression in group 2, when the samples were not treated with cytokines. Analysis of mRNA levels for these molecules after morphogen treatment revealed significant increases in both groups, which were much higher in group 1 than in group 2. The average number of IVD cells that were immunofluorescence stained positive for alkaline phosphatase increased after treatment with rhBMP-2 and TGF-β in group 1.
CONCLUSION: The biologic responsiveness to treatment of rhBMP-2, TGF-β, TNF-α, and IL-1β in the degenerative living human IVD can be different according to the degree of degeneration of the IVD.
Files in This Item:
T201500541.pdf Download
DOI
10.3349/ymj.2015.56.1.277
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kuh, Sung Uk(구성욱) ORCID logo https://orcid.org/0000-0003-2566-3209
Kim, Keun Su(김근수) ORCID logo https://orcid.org/0000-0002-3384-5638
Kim, Keung Nyun(김긍년)
Park, Jeong Yoon(박정윤) ORCID logo https://orcid.org/0000-0002-3728-7784
Cho, Yong Eun(조용은) ORCID logo https://orcid.org/0000-0001-9815-2720
Chin, Dong Kyu(진동규) ORCID logo https://orcid.org/0000-0002-9835-9294
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/139530
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