title: IL-17A enhances ADAMTS-7 expression through regulation of TNF-α in human nucleus pulposus cells.
abstract: ADMATS-7 is known to play an important role in the pathogenesis of various diseases, including cartilaginous diseases. IL-17A is an inflammatory cytokine detected in degenerative disc tissues. However, the interplay between IL-17A and ADMATS-7 in human disc degeneration is still unknown. Samples collected from 50 patients were divided into three groups according to MRI degeneration grading system score. Immunohistochemistry, RT-PCR and western Blotting were used to investigate the expression of ADAMTS-7 in NP tissues. Furthermore, a rat disc degeneration model was established, and the expression level of ADAMTS-7 was assayed using immunohistochemistry, RT-PCR and western Blotting. The human NP cells were cultured in the presence and absence of IL-17A stimulation. RNA extracts were collected, and real-time PCR was performed to determine the expression of ADAMTS-7. Moreover, ADAMTS-7 concentrations were detected in human NP cell culture supernatants by ELISA. After culturing NP cells with IL-17A (with or without Etanercept), ADAMTS-7 levels were detected in each group. ADAMTS-7 expression was dramatically elevated in both human and rat degenerative NP tissues compared with normal controls. The RT-PCR and ELISA results revealed that IL-17A could enhance the production of ADAMTS-7, while ADAMTS-7 expression dramatically decreased in the IL-17A + Etanercept group in comparison to the IL-17A alone group. Our results indicate the presence of ADAMTS-7 in human NP cells and imply its potential role in disc degeneration. Additionally, our results indicate that IL-17A induced ADAMTS-7 expression via TNF-α, which may form a molecular axis in human NP cells.
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Shuai-Shuai
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Yuan-Qiang
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Jing-kun
authors.initials: JK
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Hao-xuan
authors.initials: HX
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China. chengleiyx@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, China. forrestnie@sina.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Nie
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000071118:ADAMTS7 Protein; D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D000068800:Etanercept / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000378:metabolism* / Q000494:pharmacology; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult
chemical_list: D020381:Interleukin-17; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D000071118:ADAMTS7 Protein; C121534:ADAMTS7 protein, human; D000068800:Etanercept
keywords: ADAMTS-7; IL-17; Intervertebral disc (IVD) degeneration; TNF-α; The nucleus pulposus