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Potential Involvement of the IL-6/JAK/STAT3 Pathway in the Pathogenesis of Intervertebral Disc Degeneration.
- Source :
-
Spine [Spine (Phila Pa 1976)] 2017 Jul 15; Vol. 42 (14), pp. E817-E824. - Publication Year :
- 2017
-
Abstract
- Study Design: Laboratory study.<br />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.<br />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.<br />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.<br />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.<br />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.<br />Level of Evidence: N/A.
- Subjects :
- Adult
Aged
Animals
Annulus Fibrosus drug effects
Annulus Fibrosus pathology
Disease Models, Animal
Female
Humans
Interleukin-6 metabolism
Intervertebral Disc Degeneration physiopathology
Middle Aged
Piperidines pharmacology
Protein Kinase Inhibitors pharmacology
Pyrimidines pharmacology
Pyrroles pharmacology
Rats
Rats, Wistar
STAT3 Transcription Factor antagonists & inhibitors
Signal Transduction
Annulus Fibrosus metabolism
Interleukin-6 biosynthesis
Intervertebral Disc Degeneration metabolism
Janus Kinases metabolism
STAT3 Transcription Factor metabolism
Suppressor of Cytokine Signaling 3 Protein biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1528-1159
- Volume :
- 42
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Spine
- Publication Type :
- Academic Journal
- Accession number :
- 27879577
- Full Text :
- https://doi.org/10.1097/BRS.0000000000001982