Interleukin-1β induces angiogenesis and innervation in human intervertebral disc degeneration.
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.
Lee
Jae Man
JM
Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, Gyeonggi-do 463-712, Korea.
Song
Ji Ye
JY
Baek
MinJung
M
Jung
Hye-Young
HY
Kang
Haeyoun
H
Han
In Bo
IB
Kwon
Young Do
YD
Shin
Dong Eun
DE
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*
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