Dickkopf-related protein 1 induces angiogenesis by upregulating vascular endothelial growth factor in the synovial fibroblasts of patients with temporomandibular joint disorders

Angiogenesis has an important role in the progression of temporomandibular joint disorders (TMD). The aim of the present study was to explore the association between dickkopf-related protein 1 (DKK-1) and angiogenesis in TMD. The expression levels of DKK-1 and vascular endothelial growth factor (VEGF) were quantified by an ELISA assay of the synovial fluid from patients with TMD. The correlation between DKK-1 and VEGF was analyzed by Pearson correlation test. Synovial fibroblasts were isolated from patients with TMD and were subsequently treated with recombinant human DKK-1, anti-DKK-1 antibody, hypoxia inducible factor-1α (HIF-1α), or small interfering RNA (siRNA). The expression levels of DKK-1, HIF-1α, and VEGF were subsequently quantified. The present study also investigated the effects of DKK-1 on the migration of human umbilical vein endothelial cells (HUVEC). Increased expression levels of DKK-1 were concordant with increased expression levels of VEGF in the synovial fluid from patients with TMD. In the synovial fibroblasts, DKK-1 increased the expression levels of VEGF, and promoted HIF-1α nuclear localization. In addition, DKK-1 induced HUVEC migration, and HIF-1α siRNA inhibited DKK-1-induced cell migration. The results of the present study indicate that DKK-1 is associated with angiogenesis in the synovial fluid of patients with TMD. Furthermore, HIF-1α may be associated with DKK-1-induced HUVEC activation.