• Satoshi Suzuki, Nobuyuki Fujita, Takeshi Fujii, Kota Watanabe, Mitsuru Yagi, Takashi Tsuji, Ken Ishii, Takeshi Miyamoto, Keisuke Horiuchi, Masaya Nakamura, and Morio Matsumoto.
• *Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan †Department of Orthopaedic Surgery, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
• Spine. 2016 Nov 22.

Study DesignLaboratory study.ObjectiveTo 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 DataIL-6 plays a crucial role in IVD degeneration; however, the downstream intracellular signaling of IL-6 in the IVD is not fully understood.MethodsThe 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.ResultsA 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.ConclusionOur 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.Level Of EvidenceN/A.

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