Overloaded axial stress activates the Wnt/β-Catenin pathway in nucleus pulposus cells of adult degenerative scoliosis combined with intervertebral disc degeneration

Abstract

Background Intervertebral disc degeneration (IVDD) is the initiating factor of adult degenerative scoliosis (ADS), and ADS further accelerates IVDD, creating a vicious cycle. Nevertheless, the role of the Wnt/β-Catenin pathway in ADS combined with IVDD (ADS-IVDD) remains a mystery. Accordingly, this study was proposed to investigate the effect of axial stress on the Wnt/β-Catenin pathway in nucleus pulposus cells (NPCs) isolated from DS-IVDD patients. Methods Normal NPCs (N-NPC) were purchased and the NPCs of young (25–30 years; Y-NPC) and old (65–70 years; O-NPC) from ADS-IVDD patients were primary cultured. After treatment of NPC with overloaded axial pressure, CCK-8 and Annexin V-FITC kits were applied for detecting proliferation and apoptosis of N-NPC, Y-NPC and O-NPC, and western blotting was performed to assess the expression of Wnt 3a, β-Catenin, NPC markers and apoptosis markers (Bax, Bcl2 and Caspase 3). Results N-NPC, Y-NPC and O-NPC were mainly oval, polygonal and spindle-shaped with pseudopods, and the cell morphology tended to be flattened with age. N-NPC, Y-NPC and O-NPC were capable of synthesizing proteoglycans and expressing the NPC markers (Collagen II and Aggrecan). Notably, the expression of Wnt 3a, β-Catenin, Collagen II and Aggrecan was reduced in N-NPC, Y-NPC and O-NPC in that order. After overload axial stress treatment, cell viability of N-NPC and Y-NPC was significantly reduced, and the percentage of apoptosis and expression of Wnt 3a and β-Catenin were significantly increased. Conclusions Overloaded axial pressure activates the Wnt/β-Catenin pathway to suppress proliferation and facilitate apoptosis of NPC in ADS-IVDD patients.

S100A6 Regulates nucleus pulposus cell apoptosis via Wnt/β-catenin signaling pathway: an in vitro and in vivo study

“…With the progression of IDD, β-catenin positive cells also increase (Iwata et al 2015 ). Cai Z et al (Cai et al 2023 ) revealed that the activation of Wnt//β-catenin signaling pathway inhibits the NPCs proliferation and promote their apoptosis, thereby accelerating the progress of IDD. Shi Z et al (Shi et al 2022 ) found that high hydrostatic pressure promoted apoptosis and inhibited the viability of human NPCs by activating Wnt/β-catenin signaling pathway.…”

“…Kondo N et al (Kondo et al 2011 ) found that Wnt/β-catenin plays a key role in IVD development through Wnt/β-catenin reporter (TOPGAL) mice. Cai Z et al (Cai et al 2023 ) found that the activation of Wnt/β-catenin signaling pathway decreases the viability of NPCs and increases their apoptosis rate. Interestingly, S100A6 expression was synergistic with β-catenin in eutopic endometrial stromal cells (Liu et al 2015 ; Zhang et al 2017 ).…”