MCP‑1/CCR2 Axis Inhibits the Chondrogenic Differentiation of Human Nucleus Pulposus Mesenchymal Stem Cells

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-alpha and IL-1 beta 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.