Potential Involvement of the IL-6/JAK/STAT3 Pathway in the Pathogenesis of Intervertebral Disc Degeneration.
Spine (Phila Pa 1976)
; 42(14): E817-E824, 2017 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-27879577
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interleucina-6
/
Factor de Transcripción STAT3
/
Quinasas Janus
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Degeneración del Disco Intervertebral
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Anillo Fibroso
/
Proteína 3 Supresora de la Señalización de Citocinas
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Adult
/
Aged
/
Animals
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Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Spine (Phila Pa 1976)
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón