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

Jiang SJ, Li W, Li YJ, Fang W, Long X - Mol Med Rep (2015)

Bottom Line: The present study also investigated the effects of DKK‑1 on the migration of human umbilical vein endothelial cells (HUVEC).In addition, DKK‑1 induced HUVEC migration, and HIF‑1α siRNA inhibited DKK‑1‑induced cell migration.Furthermore, HIF‑1α may be associated with DKK‑1‑induced HUVEC activation.

View Article: PubMed Central - PubMed

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.

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.

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Elevated expression levels of dickkopf-related protein 1 (DKK-1) are associated with increased expression levels of vascular endothelial growth factor (VEGF) in the synovial fluid of patients with temporomandibular joint disorder (TMD). (A) The expression levels of DKK-1 in both the control group (n=7) and TMD group (n=56); **P<0.01; Student's t-test. (B) The expression levels of DKK-1 in the control group (n=7) and the following patient groups: The anterior disc displacement with reduction (ADDwR, n=22), the anterior disc displacement without reduction (ADDw/oR, n=22), and the osteoarthritis (OA, n=12) group [*P<0.05, and ***P<0.001; two-way analysis of variance (ANOVA)]. (C) The expression levels of VEGF in both the control group (n=7) and TMD group (n=56 samples); ***P<0.001; Student's t-test. (D) The expression levels of VEGF in the control group (n=7) and the following patient groups: The anterior disc displacement (ADD, n=44) and the OA group (n=12) (*P<0.05, and ***P<0.001; two-way ANOVA). (E) Association between the expression levels of DKK-1 and VEGF, as determined by a Pearson correlation test.
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f1-mmr-12-04-4959: Elevated expression levels of dickkopf-related protein 1 (DKK-1) are associated with increased expression levels of vascular endothelial growth factor (VEGF) in the synovial fluid of patients with temporomandibular joint disorder (TMD). (A) The expression levels of DKK-1 in both the control group (n=7) and TMD group (n=56); **P<0.01; Student's t-test. (B) The expression levels of DKK-1 in the control group (n=7) and the following patient groups: The anterior disc displacement with reduction (ADDwR, n=22), the anterior disc displacement without reduction (ADDw/oR, n=22), and the osteoarthritis (OA, n=12) group [*P<0.05, and ***P<0.001; two-way analysis of variance (ANOVA)]. (C) The expression levels of VEGF in both the control group (n=7) and TMD group (n=56 samples); ***P<0.001; Student's t-test. (D) The expression levels of VEGF in the control group (n=7) and the following patient groups: The anterior disc displacement (ADD, n=44) and the OA group (n=12) (*P<0.05, and ***P<0.001; two-way ANOVA). (E) Association between the expression levels of DKK-1 and VEGF, as determined by a Pearson correlation test.

Mentions: To determine the expression levels of DKK-1 in the synovial fluid of patients with TMD, the synovial fluid from 50 patients and seven healthy controls were collected for analysis. The expression levels of DKK-1 in the patients with TMD were significantly higher, as compared with the control subjects (P<0.01 Fig. 1A). The expression levels of DKK-1 in the TMD-OA group were significantly higher, as compared with those of the TMD-ADDwR and TMD-ADDw/oR groups (P<0.05), and with those of the control group (P<0.001, Fig. 1B). The expression levels of DKK-1 in the synovial fluid of the TMD-ADDw/oR group was significantly increased, as compared with those of the control group (P<0.05, Fig. 1B). However, the difference between the mean expression levels of DKK-1 in patients with TMD-ADDwR and the control subjects was not significant (Fig. 1B). As shown in Fig. 1C, the expression levels of VEGF in the synovial fluid of patients with TMD was significantly higher, as compared with the control group (P<0.001). The expression levels of VEGF in the OA group were significantly higher, as compared with the ADD groups (P<0.05) and control group (P<0.001, Fig. 1D). The expression levels of VEGF in the TMD-ADDwR group and TMD-ADDw/oR group were not significantly different, as compared with the control group (data not shown). Furthermore, the expression levels of DKK-1 were positively associated with higher expression levels of VEGF (P<0.05, r=0.2947, n=63, Fig. 1E). These results suggest that the expression levels of DKK-1 are significantly increased in the synovial fluid of patients with TMD, and that DKK-1 expression may have an important role in TMD angiogenesis.


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

Jiang SJ, Li W, Li YJ, Fang W, Long X - Mol Med Rep (2015)

Elevated expression levels of dickkopf-related protein 1 (DKK-1) are associated with increased expression levels of vascular endothelial growth factor (VEGF) in the synovial fluid of patients with temporomandibular joint disorder (TMD). (A) The expression levels of DKK-1 in both the control group (n=7) and TMD group (n=56); **P<0.01; Student's t-test. (B) The expression levels of DKK-1 in the control group (n=7) and the following patient groups: The anterior disc displacement with reduction (ADDwR, n=22), the anterior disc displacement without reduction (ADDw/oR, n=22), and the osteoarthritis (OA, n=12) group [*P<0.05, and ***P<0.001; two-way analysis of variance (ANOVA)]. (C) The expression levels of VEGF in both the control group (n=7) and TMD group (n=56 samples); ***P<0.001; Student's t-test. (D) The expression levels of VEGF in the control group (n=7) and the following patient groups: The anterior disc displacement (ADD, n=44) and the OA group (n=12) (*P<0.05, and ***P<0.001; two-way ANOVA). (E) Association between the expression levels of DKK-1 and VEGF, as determined by a Pearson correlation test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4581813&req=5

f1-mmr-12-04-4959: Elevated expression levels of dickkopf-related protein 1 (DKK-1) are associated with increased expression levels of vascular endothelial growth factor (VEGF) in the synovial fluid of patients with temporomandibular joint disorder (TMD). (A) The expression levels of DKK-1 in both the control group (n=7) and TMD group (n=56); **P<0.01; Student's t-test. (B) The expression levels of DKK-1 in the control group (n=7) and the following patient groups: The anterior disc displacement with reduction (ADDwR, n=22), the anterior disc displacement without reduction (ADDw/oR, n=22), and the osteoarthritis (OA, n=12) group [*P<0.05, and ***P<0.001; two-way analysis of variance (ANOVA)]. (C) The expression levels of VEGF in both the control group (n=7) and TMD group (n=56 samples); ***P<0.001; Student's t-test. (D) The expression levels of VEGF in the control group (n=7) and the following patient groups: The anterior disc displacement (ADD, n=44) and the OA group (n=12) (*P<0.05, and ***P<0.001; two-way ANOVA). (E) Association between the expression levels of DKK-1 and VEGF, as determined by a Pearson correlation test.
Mentions: To determine the expression levels of DKK-1 in the synovial fluid of patients with TMD, the synovial fluid from 50 patients and seven healthy controls were collected for analysis. The expression levels of DKK-1 in the patients with TMD were significantly higher, as compared with the control subjects (P<0.01 Fig. 1A). The expression levels of DKK-1 in the TMD-OA group were significantly higher, as compared with those of the TMD-ADDwR and TMD-ADDw/oR groups (P<0.05), and with those of the control group (P<0.001, Fig. 1B). The expression levels of DKK-1 in the synovial fluid of the TMD-ADDw/oR group was significantly increased, as compared with those of the control group (P<0.05, Fig. 1B). However, the difference between the mean expression levels of DKK-1 in patients with TMD-ADDwR and the control subjects was not significant (Fig. 1B). As shown in Fig. 1C, the expression levels of VEGF in the synovial fluid of patients with TMD was significantly higher, as compared with the control group (P<0.001). The expression levels of VEGF in the OA group were significantly higher, as compared with the ADD groups (P<0.05) and control group (P<0.001, Fig. 1D). The expression levels of VEGF in the TMD-ADDwR group and TMD-ADDw/oR group were not significantly different, as compared with the control group (data not shown). Furthermore, the expression levels of DKK-1 were positively associated with higher expression levels of VEGF (P<0.05, r=0.2947, n=63, Fig. 1E). These results suggest that the expression levels of DKK-1 are significantly increased in the synovial fluid of patients with TMD, and that DKK-1 expression may have an important role in TMD angiogenesis.

Bottom Line: The present study also investigated the effects of DKK‑1 on the migration of human umbilical vein endothelial cells (HUVEC).In addition, DKK‑1 induced HUVEC migration, and HIF‑1α siRNA inhibited DKK‑1‑induced cell migration.Furthermore, HIF‑1α may be associated with DKK‑1‑induced HUVEC activation.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus