Follistatin‐Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF‐<i>α</i> and Smad Signaling Pathway
Shaoyi Wang, Jianlu Wei, Jie Shi, Qiting He, Xiaocong Zhou, Ximei Gao, Lei Cheng
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.