Intervertebral disc degeneration (Idd) is a condition involving disruption of the bone tissue distribution. Nucleus pulposus mesenchymal stem cells (NPMScs) and Sirtuin 1 (SIRT1) play important roles in bone diseases, therefore the aim of the present study was to evaluate the roles of SIRT1 and NPMScs in Idd. First, NPMScs were harvested from patients with Idd. Then, the NPMScs were treated with a SIRT activator, and monocyte chemoattractant protein 1 (McP1) and chemokine receptor 2 (ccR2) inhibitors. Indices related to NPMSc growth, proliferation, differentiation and apoptosis were measured. Subsequently, Idd rat models were established and were transfected with NPMScs overexpressing SIRT1. NPMSc apoptosis and cartilage differentiation were detected in the rat Idd model. SIRT1 expression was found to be decreased, and the expression of McP1 and ccR2 increased in NPMScs of patients with Idd. The upregulation of SIRT1 and the downregulation of the McP1/ccR2 axis promoted cartilage differentiation and reduced the number of apoptotic NPMScs. Furthermore, McP1 reversed the progression of the cartilage differentiation of NPMScs and the inhibition of NPMSc apoptosis induced by SIRT1 overexpression. Moreover, the transplantation of rat NPMScs overexpressing SIRT1 relieved Idd in rats. Therefore, SIRT1 overexpression improved cartilage differentiation and reduced the apoptosis of NPMScs by inactivating the McP1/ccR2 axis, thus attenuating Idd in rats.
intervertebral disc degeneration (idd) creates a hostile environment with high osmotic pressure, high mechanical stress, hypoxia and a low pH, where cytokines such as TnF-α and il-1β are highly expressed. The degenerating intervertebral disc has high local expression of monocyte chemoattractant protein-1 (McP-1), which is associated with the degree of degeneration. However, there are a few reports on the influence of MCP-1 on nucleus pulposus-derived stem cells (NPSCs). In the present study, a significant upregulation of McP-1 was observed in nPScs cultured in vitro with pro-inflammatory cytokines. MCP-1 significantly inhibited the migration and proliferation of nPScs in a dose-dependent manner as detected via cell counting Kit-8, wound healing and Transwell assays. Western blotting and histological analysis demonstrated that MCP-1 significantly reduced chondrogenic nPSc differentiation. reverse transcription-quantitative Pcr and western blotting revealed that c-c chemokine receptor type 2 (ccr2) mrna and protein expression levels were significantly enhanced by McP-1. Furthermore, McP-1 significantly inhibited the migration, differentiation and proliferation of nPScs, which was effectively reversed by blocking ccr2 with the inhibitor rS504393. overall, these results demonstrated that McP-1 may contribute to the inhibition of chondrogenic nPSc differentiation via McP-1/ccr2 chemotaxis signals, providing a potential therapeutic target for idd.
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