title: Dickkopf‑related protein 1 induces angiogenesis by upregulating vascular endothelial growth factor in the synovial fibroblasts of patients with temporomandibular joint disorders.
abstract: 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.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Jiang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Long
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D013705:Temporomandibular Joint Disorders / Q000235:genetics*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: C501126:DKK1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A