| First Author | Wang S | Year | 2021 |
| Journal | Oxid Med Cell Longev | Volume | 2021 |
| Pages | 6640751 | PubMed ID | 33936382 |
| Mgi Jnum | J:329465 | Mgi Id | MGI:6809735 |
| Doi | 10.1155/2021/6640751 | Citation | Wang S, et al. (2021) Follistatin-Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF-alpha and Smad Signaling Pathway. Oxid Med Cell Longev 2021:6640751 |
| abstractText | 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-alpha-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-alpha response and Smad pathway activity and ultimately delayed IDD. |
