Involvement of SDF ‐1 and monocyte chemoattractant protein‐1 in hydrogen peroxide‐induced extracellular matrix degradation in human dental pulp cells

Aim To determine whether chemokines such as SDF ‐1 and monocyte chemoattractant protein‐1 ( MCP ‐1) are responsible for hydrogen peroxide ( H 2 O 2 )‐induced extracellular matrix ( ECM ) degradation and to identify the underlying mechanism in human dental pulp cells ( HDPC s). Method Human dental pulp cells were exposed to 0.4 mmol H 2 O 2 for 48 h. m RNA expression and protein expression were examined by RT ‐ PCR and W estern blot analysis, respectively. The m RNA expression of chemokine ( SDF ‐1 and MCP ‐1), their receptors ( CXCR 4 and CXCR 2) and extracellular matrix proteins was evaluated by reverse transcriptase‐polymerase chain reaction. The production of SDF ‐1, MCP ‐1, CXCR 4 and CCR 2 in the culture medium was determined by enzyme‐linked immunosorbent assay. Signal transduction pathway was examined by W estern blotting. Results Hydrogen peroxide provoked the activation of MCP ‐1 and SDF ‐1 m RNA and their respective receptors, CXCR 4 and CXCR 2. H 2 O 2 treatment concomitantly downregulated the expression of ECM molecules, such as type I collagen, elastin and fibronectin, and upregulated the m RNA expression of matrix metalloproteinase‐1 ( MMP ‐1), MMP ‐2, MMP ‐8 and MMP ‐9. Hydrogen peroxide‐induced ECM degradation and MMP upregulation were blocked by neutralizing antibodies and si RNA s directed against SDF ‐1 and MCP ‐1. Inhibition of SDF ‐1 and MCP ‐1 blocked the H 2 O 2 ‐induced activation of Akt, p38, ERK and NF ‐k B . Conclusion Inhibition of SDF and MCP ‐1 is a potent component of reducing release reactive oxygen species‐induced ECM degradation in HDPC s and may play an important role in pulpal and periapical inflammation.