Follistatin-Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF-α and Smad Signaling Pathway.
Oxid Med Cell Longev
; 2021: 6640751, 2021.
Article
em En
| MEDLINE
| ID: mdl-33936382
ABSTRACT
BACKGROUND:
Inflammation plays an important role in intervertebral disc degeneration (IDD). The protein follistatin-like 1 (FSTL1) plays a proinflammatory role in a variety of inflammatory diseases.OBJECTIVES:
The purpose of this study was to investigate whether IDD could be delayed by inhibiting FSTL-1 expression.METHODS:
We established a puncture-induced IDD model in wild-type and FSTL-1+/- mice and collected intervertebral discs (IVDs) from the mice. Safranin O staining was used to detect cartilage loss of IVD tissue, and HE staining was used to detect morphological changes of IVD tissue. We measured the expression of FSTL-1 and related inflammatory indicators in IVD tissues by immunohistochemical staining, real-time PCR, and Western blotting.RESULTS:
In the age-induced model of IDD, the level of FSTL-1 increased with the exacerbation of degeneration. In the puncture-induced IDD model, FSTL-1-knockdown mice showed a reduced degree of degeneration compared with that of wild-type mice. Further experiments showed that FSTL-1 knockdown also significantly reduced the level of related inflammatory factors in IVD. In vitro experiments showed that FSTL-1 knockdown significantly reduced TNF-α-induced inflammation. Specifically, the expression levels of the inflammatory factors COX-2, iNOS, MMP-13, and ADAMTS-5 were reduced. Knockdown of FSTL-1 attenuated inflammation by inhibiting the expression of P-Smad1/5/8, P-Erk1/2, and P-P65.CONCLUSION:
Knockdown of FSTL-1 attenuated inflammation by inhibiting the TNF-α response and Smad pathway activity and ultimately delayed IDD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article