title: Interleukin-1β induces angiogenesis and innervation in human intervertebral disc degeneration.
abstract: Degenerative disorders of the intervertebral discs (IVDs) are generally characterized by enhanced matrix degradation, angiogenesis, innervation, and increased expression of catabolic cytokines. In this study, we investigated the effects of inflammatory cytokines, IL-1β, and TNF-α, on the expression of an angiogenic factor, vascular endothelial growth factor (VEGF), and neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in human IVD degeneration. IL-1β and TNF-α stimulated the gene expression of VEGF, NGF, and BDNF in nucleus pulposus (NP) cells isolated from patient tissues. Immunohistochemical results demonstrated a positive correlation between IL-1β and VEGF/NGF/BDNF expression in human IVD tissues. RNA expression analysis of patient tissues also identified positive correlations between VEGF and platelet endothelial cell adhesion molecule-1 (PECAM-1) and between NGF/BDNF and protein gene product 9.5 (PGP9.5). Our findings suggest that IL-1β is generated during IVD degeneration, which stimulates the expression of VEGF, NGF, and BDNF, resulting in angiogenesis and innervation.
authors.affiliation: Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, Gyeonggi-do 463-712, Korea.
authors.forename: Jae Man
authors.initials: JM
authors.lastname: Lee
authors.forename: Ji Ye
authors.initials: JY
authors.lastname: Song
authors.forename: MinJung
authors.initials: M
authors.lastname: Baek
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Haeyoun
authors.initials: H
authors.lastname: Kang
authors.forename: In Bo
authors.initials: IB
authors.lastname: Han
authors.forename: Young Do
authors.initials: YD
authors.lastname: Kwon
authors.forename: Dong Eun
authors.initials: DE
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D020932:Nerve Growth Factor / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C508585:IL1B protein, human; D053583:Interleukin-1beta; C502240:NGF protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; C482860:UCHL1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D043222:Ubiquitin Thiolesterase