Up-regulation of vascular endothelial growth factor in synovial fibroblasts from human temporomandibular joint by hypoxia

INTRODUCTION: Enhanced expression of vascular endothelial growth factor (VEGF) has been described in patients with internal derangement (ID). Herein, we examined the expression of VEGF in synovial fibroblasts from temporomandibular joint (TMJ) under hypoxia and investigated the regulation of hypoxia-inducible factor-1alpha (HIF-1alpha) involved in the expression of VEGF. METHODS: Synovial fibroblasts were prepared from human TMJ. These cells were incubated under hypoxia or normoxia for the indicated time periods. VEGF levels in cultured supernatant were measured by an ELISA. VEGF mRNA isoforms and stability were assessed using RT-PCR and Northern blot analysis respectively. HIF-1alpha accumulation was evaluated by Western blotting and immunofluorescence. RESULTS: VEGF were significantly induced by hypoxia in synovial fibroblasts. In response to hypoxia, VEGF121 and VEGF165 mRNA were both remarkably increased, while there was no change in VEGF mRNA stability. The accumulation and nuclear translocation of HIF-1alpha occurred under hypoxia. CONCLUSIONS: Hypoxia may mainly induce the expression of VEGF121 and VEGF165 in synovial fibroblasts to promote inflamed angiogenesis of TMJ. HIF-1alpha, which is clearly activated in response to hypoxia, may control the expression of VEGF in synovial fibroblasts from TMJ.