Abstract
BackgroundFailed back surgery syndrome (FBSS) is a common complication after the laminectomy. Epidural fibrosis is the major cause of lower back pain and other complications. Numerous studies have shown that apigenin (API) could treat various fibrotic diseases by regulating various signaling pathways, whereas no study has discussed whether API can inhibit fibroblast proliferation and reduce epidural fibrosis after the laminectomy by regulating Wnt3a/β-catenin signaling pathway.MethodsHuman fibroblasts were cultured and treated with API in different concentrations for 24 h. CCK-8 detection and EdU incorporation assay were performed to detect cell viability and cell proliferation. Western blotting analysis was applied to detect expressions of proliferative proteins, Wnt3a, and its downstream proteins. Moreover, the Wnt3a gene was overexpressed in fibroblasts to define the relationship between Wnt3a/β-catenin signaling pathway and fibroblast proliferation. Wnt3a overexpressed fibroblasts were treated with API to verify if it could reverse the effects of API treatment. Twenty-four Sprague-Dawley rats were randomly divided into four groups. Laminectomy was performed and the rats were gavaged with different doses of API or 5% sodium carboxyl methyl cellulose (CMC-Na) solution for 1 month. The abilities of API to inhibit fibroblast proliferation and to reduce epidural fibrosis were evaluated using histological and immunohistochemical analysis.ResultsCCK-8 detection and EdU incorporation assay demonstrated that API could inhibit the viability and proliferation rate of fibroblasts in a concentration-dependent manner. The Western blotting analysis revealed that API could inhibit the expressions of PCNA, cyclinD1, Wnt3a, and its downstream proteins. The overexpression of Wnt3a in fibroblasts could upregulate the expressions of proliferative proteins such as PCNA and cyclinD1. The inhibitory effect of API on PCNA, Wnt3a, and its downstream proteins was partially reversed by overexpression of Wnt3a. Moreover, the results of the histological and immunohistochemical analysis revealed that API could reduce the epidural fibrosis in rats by inhibiting fibroblast proliferation in a dose-dependent manner.ConclusionsAPI can inhibit fibroblast proliferation and reduce epidural fibrosis by suppressing Wnt3a/β-catenin signaling pathway, which can be adopted as a new option to prevent epidural fibrosis after the laminectomy.
Highlights
Failed back surgery syndrome (FBSS) is a common complication after the laminectomy
The results revealed that API inhibited fibroblast proliferation in a concentrationdependent manner
The inhibitory effect of API on Proliferating cell nuclear antigen (PCNA), Wnt3a, and its downstream proteins was partially reversed by overexpression of Wnt3a (Fig. 2e, f)
Summary
Failed back surgery syndrome (FBSS) is a common complication after the laminectomy. Epidural fibrosis is the major cause of lower back pain and other complications. Numerous studies have shown that apigenin (API) could treat various fibrotic diseases by regulating various signaling pathways, whereas no study has discussed whether API can inhibit fibroblast proliferation and reduce epidural fibrosis after the laminectomy by regulating Wnt3a/β-catenin signaling pathway. Failed back surgery syndrome (FBSS) is considered as a serious condition primarily caused by epidural fibrosis after laminectomy. Numerous previous studies indicate that the epidural fibrosis primarily produced by excessive fibroblast proliferation can extend into the neural canal and adhere to the dura mater, which often result in the pain of leg and lumbago [5,6,7]. Given the safety of various drugs, those with a significant effect on preventing fibrosis and without obvious toxicity have been constantly explored for clinical application
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