Follistatin-Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice Through Interacting with TNF- and Smad Signaling Pathway

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2021 May 3

PMID 33936382

Citations 10

Authors

Shaoyi Wang

Jianlu Wei

Jie Shi

Qiting He

Xiaocong Zhou

Ximei Gao

Lei Cheng

Affiliations

Soon will be listed here.

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--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- response and Smad pathway activity and ultimately delayed IDD.

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