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

• Published in: Oxidative medicine and cellular longevity 2021, Vol.2021 (1), p.6640751-6640751
• Main Authors: Wang, Shaoyi, Wei, Jianlu, Shi, Jie, He, Qiting, Zhou, Xiaocong, Gao, Ximei, Cheng, Lei
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis Regulatory Proteins - metabolism; Autoimmune diseases; Back pain; Binding sites; Cybernetics; Cytokines; Degenerative disc disease; Disease Models, Animal; Experiments; Follistatin - metabolism; Humans; Inflammation; Intervertebral Disc Degeneration - drug therapy; Laboratory animals; Male; Mice; Mitochondrial Proteins - metabolism; Proteins; Rheumatoid arthritis; Signal Transduction; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2021/6640751

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.