MCP‑1/CCR2 axis inhibits the chondrogenic differentiation of human nucleus pulposus mesenchymal stem cells.

Abstract

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 invitro 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‑Cchemokine receptor type2(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.