Study On The Function Of DKK-1 In Temporomandibular Joint Osteoarthritis

Part1. The expression of DKK-1 in the synovial membrane from osteoarthritisObjective:It has been reported that DKK-1 plays essential roles in the progression of caner, rheumatic. The aim of this part was to explore the the expression of DKK-1 in the synovial membrane from osteoarthritisMethods:The expression of DKK-1 was analyzed by IHC in the synovial membrane from osteoarthritisResults:DKK-1 could be detected in the most of case.The distribution of DKK-1 in synovial tissue DKK-1 positive cases presented a membranous pattern and nuclear pattern in OA group and in normal group. In the interstitial tissues, DKK-1 was presented slightly staining. DKK-1 positive cell counts and value of staining in OA group was more higher than those in normal group. DKK-1 also highly expressed in the inner epithelial ductal cells in OA group.The expression of DKK-1 in OA group was significantly much higher than that in normal group.Conclusions:The expression of DKK-1 in osteoarthritis group was much higher.Part2. The expression of DKK-1 and VEGF in the synovia from temporomandibular joint diseaseObjective:The protein in synovia may serve as monitor for the synovial cell pathology, physiology reaction. The aim of this part was to investigate expression of DKK-1 and VEGF in the synovia from temporomandibular joint disease and to analysis the relationship between these two proteins.Methods:synovial fluid were harvested from the volunteers and patients with anterior disc displacement with reduction and osteoarthritis. ELISA was performed to detect the expression of DKK-1 and VEGF in the synovia.Results:Increased expression of DKK-1 is related to VEGF in the synovial fluid from temporomandibular joint disorders. The expression of DKK-1 and VEGF in the TMD-OA group was significantly higher than that in the TMD-ADDwR and TMD-ADDw/oR groups (P<0.05) and control group. Compared to the control group, DKK-1 and VEGF in synovial fluid from the TMD-ADDw/oR group was increased.Conclusions:Increased expression of DKK-1 is related to VEGF in the synovial fluid from temporomandibular joint disorders DKK-1 plays essential roles in the angiogenesis in osteoarthritis.Part3. The mechanisms of DKK-1 inducing angiogenesis in vitroObjective:The aim of this part was to analyze the effects of DKK-1 on angiogenesis in vitro using primary cell.Methods:In inflammation condition, the expression of DKK-1 was detected by western blot. DKK-1 monoclone antibody and exogenous DKK-1 were exerted to measure the effects of DKK-1 on the expression of VEGF. HIF-la siRNA was used for detection of the expression of VEGF after exogenous DKK-1 treatment. Finally, the indirect co-culture system between HUVECs and synovial cell was establsiehd using conditioned medium (CM) to explore the effects of DKK-1 on HUVECs migration and tube formation.Results:DKK-1 increased inflammation-induced VEGF expression in synovial fibroblasts. HIF-la mediated DKK-1 regulation of VEGF expression. HIF-la siRNA inhibit DKK-1-induced increase of HUVEC migration.Conclusions:DKK-1 could promote the angiogenesis via activation of HIF-la signaling pathways.