Potential Involvement of the IL-6/JAK/STAT3 Pathway in the Pathogenesis of Intervertebral Disc Degeneration

Satoshi Suzuki, Nobuyuki Fujita, Takeshi Fujii, Kota Watanabe, Mitsuru Yagi, Takashi Tsuji, Ken Ishii, Takeshi Miyamoto, Keisuke Horiuchi, Masaya Nakamura, Morio Matsumoto

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Abstract

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.Level of Evidence: N/A

Original languageEnglish
JournalSpine
DOIs
Publication statusAccepted/In press - 2016 Nov 22

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ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Clinical Neurology

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