Abstract
Aberrant apoptosis of nucleus pulposus cells (NPCs) is one of the most remarkable pathological changes in intervertebral disc degeneration (IDD) development. Albeit the advances in the application of stem cell-based therapy in IDD treatment, the molecular mechanisms underlying the anti-apoptotic actions of mesenchymal stem cell (MSC) remain poorly elucidated. The expression patterns of apoptosis-related proteins and Wnt/β-catenin-related genes in NP samples isolated from patients with mild or severe IDD were compared by performing immunoblot assay and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. NPCs were in vitro treated with compression to induce apoptosis and then co-cultured with Wharton's Jelly-derived MSCs without direct interaction. After that, flow cytometry was carried out to detect the apoptosis rate of NPCs and the activity of Wnt/β-catenin pathway was determined. DKK-1 was used to inhibit Wnt signaling, in prior to evaluation of the effects of WJ-MSCs on apoptosis within the co-cultured NPCs. Compared to the mild IDD group, there was a significant increase in the expression of Caspase-3 and Bax in the NP tissues from severe IDD patients, whereas Bcl-2 displayed an opposite result. In addition, the expression of Wnt 3a, Wnt 5a, Wnt 10a, GSK-3β, cyclinD1 and β-catenin was notably augmented in parallel with IDD progression. After compression treatment, the proportion of apoptotic NPCs was increased, which was then dramatically reversed by WJ-MSCs co-culture. Likewise, WJ-MSCs suppressed compression-induced Wnt-related gene expression and blocking Wnt/β-catenin pathway using DKK-1 enhanced the anti-apoptotic impacts of WJ-MSCs. In the presence of DKK-1, there was no significant difference between NPCs co-cultured with WJ-MSCs and those cells cultured alone. WJ-MSCs attenuate the compression-induced apoptosis in NPCs and inhibit the activation of Wnt/β-catenin signaling. Blocking Wnt/β-catenin pathway further facilitates the actions of WJ-MSCs in anti-apoptosis, indicating that Wnt/β-catenin signaling plays a crucial role in this process and may function as a potential therapeutic target for IDD treatment.
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