TY - JOUR
T1 - Potential Involvement of the IL-6/JAK/STAT3 Pathway in the Pathogenesis of Intervertebral Disc Degeneration
AU - Suzuki, Satoshi
AU - Fujita, Nobuyuki
AU - Fujii, Takeshi
AU - Watanabe, Kota
AU - Yagi, Mitsuru
AU - Tsuji, Takashi
AU - Ishii, Ken
AU - Miyamoto, Takeshi
AU - Horiuchi, Keisuke
AU - Nakamura, Masaya
AU - Matsumoto, Morio
N1 - Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc.
PY - 2017/7/15
Y1 - 2017/7/15
N2 - Study Design. 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. Summary of Background Data. 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. Conclusion. 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.
AB - Study Design. 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. Summary of Background Data. 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. Conclusion. 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.
KW - Cytokine signaling
KW - Janus kinase
KW - interleukin-6
KW - intervertebral disc degeneration
KW - pathogenesis
KW - signal transducers
UR - https://www.scopus.com/pages/publications/84996772860
UR - https://www.scopus.com/pages/publications/84996772860#tab=citedBy
U2 - 10.1097/BRS.0000000000001982
DO - 10.1097/BRS.0000000000001982
M3 - Article
C2 - 27879577
AN - SCOPUS:84996772860
SN - 0362-2436
VL - 42
SP - E817-E824
JO - Spine
JF - Spine
IS - 14
ER -