title: IL-21 Is Positively Associated with Intervertebral Disc Degeneration by Interaction with TNF-α Through the JAK-STAT Signaling Pathway.
abstract: This study was conducted in order to investigate the function of IL-21 in intervertebral disc degeneration. The serum concentration of IL-21 in patients with lumbar disc herniation (LDH) was examined by ELISA. Immunohistochemistry and western blot analysis were performed to detect the expression of IL-21, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-7), and tumor necrosis factor alpha (TNF-α) in degenerated intervertebral disc (IVD) tissues of human and rat. Moreover, nucleus pulposus (NP) cells were treated with 0, 10, 100, and 1000 ng/mL of IL-21 cytokine with and without AG490. TNF-α, ADAMTS-7, and matrix metalloproteinases-13 (MMP-13) mRNA expression was determined by RT-PCR. The expression of signal transducers and activators of transcription, STAT-1, STAT-3, and STAT-5b, was detected by western blot. IL-21 concentration level is higher in the degenerated group and positively correlates with the visual analog score (VAS). IL-21, ADAMTS-7, and TNF-α can be detected in the degenerative NP tissues in both human and rat degenerated NP tissues. The mRNA expression of ADAMTS-7, TNF-α, and MMP-13 was enhanced after stimulation with IL-21. Compared to control, STAT-1, STAT-3, and STAT-5b expression was also enhanced after IL-21 treatment, with STAT-3 being the most significantly enhanced; furthermore, expression was significantly reduced after treatment with AG490. The mRNA expression of TNF-α was markedly reduced after treatment with AG490 compared to treatment with IL-21 only. IL-21 is involved in the pathological development of IVD degeneration and IL-21 could aggravate IVD degeneration by stimulating TNF-α through the STAT signaling pathway.
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: YuanQiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: JingKun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: KaiYuan
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, People's Republic of China. chengleiyx@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007378:Interleukins / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D055959:Intervertebral Disc Degeneration / Q000209:etiology* / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000070614:Nucleus Pulposus / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D050791:STAT Transcription Factors / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D053612:Janus Kinases; D000098546:Interleukin-21
keywords: ADAMTS-7; IL-21; STAT; TNF-α; inflammation; lumbar disc herniation