The Role of Polylactic-Coglycolic Acid-Coated Electrospinning Nanoscaffold-Mediated Wnt/β-Catenin Signaling Pathway in Intervertebral Disc Degeneration and Its Relationship with Vitamin D Receptor

Abstract

Using polyvinyl alcohol (PVA), polylactic coglycolic acid (PLGA), and transforming growth factor-β (TGF-β1) as raw materials, PLGA-coated electrospun nanoscaffold (ESNS) PVA-TGF-β1@PLGA was prepared by the coaxial ES method. Its characterization was analyzed by scanning electron microscopy (SEM), high-performance liquid chromatography (HPLC), and Fourier transform infrared spectroscopy (FTIR). Seventy-five healthy New Zealand rabbits were randomly rolled into the control group (no treatment, group C), model group (intervertebral disc degeneration (IDD) model, group M), and nanofiber scaffold group (implant PVA- TGF-β1@PLGA, group P). HE staining was adopted to visualize the histological morphology of the intervertebral disc (IVD) endplate in the different groups. Sox-9, Collagen type II, and Aggrecan genes in different groups of IVD endplate tissues were detected by qPCR. Vascular endothelial growth factor (VEGF), Wnt3α, β-catenin, glycogen synthase kinase-3β (GSK-3β), and vitamin D receptor (VDR) protein in IVD endplate tissues of different groups was detected by immunohistochemistry. IVD VDR protein and IDD-related protein levels were detected by Western blot. Linear trend tests and correlations were adopted to analyze the relationship between different degrees of IDD and VDR level. The results showed that the average particle size of the PVA-TGF-β1@PLGA NSs was approximately 415 nm, and Fourier infrared detection proved that PVA-TGF-β1@PLGA NSs were prepared. Sox-9, Collagen Type II, and Aggrecan gene levels in group M were notably inferior to those in group C (P < 0.05). Sox-9, collagen type II, and aggrecan gene levels in group P were substantially increased versus group M (P < 0.05). β-catenin level in groups P and M was greatly superior to that in group C (P < 0.05). GSK-3β and VEGF levels in group P were increased relative to group M (P < 0.05), while that of Wnt3α was decreased (P < 0.05). Western blotting confirmed that there was a negative relationship between the expression of IDD-related proteins and VDR. The results showed that PLGA-coated ESNS could promote Collagen II expression in the matrix of the nucleus pulposus (NP), reduce proteoglycan loss, and promote cell proliferation and differentiation by regulating the Wnt/β-catenin signaling pathway (Wnt/β Sig). VDR level was negatively correlated with the development of IDD in rats.