title: Potential Involvement of the IL-6/JAK/STAT3 Pathway in the Pathogenesis of Intervertebral Disc Degeneration.
abstract: METHODS
  Laboratory study.
  
  
  OBJECTIVE
  To elucidate the potential involvement of the interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducers and activator of transcription (STAT3) pathway in the development of intervertebral disc (IVD) degeneration.
  
  
  BACKGROUND
  IL-6 plays a crucial role in IVD degeneration; however, the downstream intracellular signaling of IL-6 in the IVD is not fully understood.
  
  
  METHODS
  The expression levels of IL-6 and suppressors of cytokine signaling 3 (SOCS3), a target gene of the IL-6/JAK/STAT3 pathway, were evaluated in rat and human degenerated IVD samples. The effects of IL-6 on primary rat annulus fibrosus (AF) cells were analyzed using quantitative PCR, immunocytochemistry, and Western blotting. The potential efficacy of a JAK inhibitor, CP690,550, in neutralizing the effect of IL-6 was evaluated in vitro.
  
  
  RESULTS
  A high expression of IL-6 and SOCS3 was observed in both rat and human degenerated IVD samples. In rat AF cells, IL-6 markedly induced the phosphorylation of STAT3 and the expression of cyclooxygenase-2 and matrix metalloprotease-13. CP690,550 significantly suppressed the phosphorylation of STAT3 and offset the catabolic effect of IL-6 in rat AF cells.
  
  
  CONCLUSIONS
  Our results suggest that the IL-6/JAK/STAT3 pathway is involved in the pathogenesis of IVD degeneration and that CP690,550 suppresses the catabolic effect of the IL-6 in the IVD.
  
  
  METHODS
  N/A.
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fujita
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yagi
authors.affiliation: Department of Orthopedic Surgery, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Horiuchi
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000070616:Annulus Fibrosus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000503:physiopathology; D053612:Janus Kinases / Q000378:metabolism*; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; C479163:tofacitinib; D053612:Janus Kinases