Resveratrol Promotes Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Through miR-193a/SIRT7 Axis.

Resveratrol (RES) is a novel dietary phenol compound derived from plants and has been studied extensively for its health benefit and medical potential including osteoporosis. The purpose of this study is to investigate the role of resveratrol in osteoporosis in vivo and in vitro and explore the mechanism of osteogenic differentiation of BMSCs. RT-qPCR, ELISA, and Western blot were used to measure the expression level of miR-193a, SIRT7, and osteogenic markers proteins. The interaction between miR-193a and SIRT7 was validated by dual-luciferase reporter assay. Moreover, MTT assay was conducted to detect cell viability. Alizarin red s staining was used to examine bone formation and calcium deposits. The ovariectomized rat model was set up successfully and HE staining was used to examine femoral trabeculae tissue. Our results showed that miR-193a was overexpressed, while SIRT7 was downregulated in osteoporosis. RES suppressed miR-193a to promote osteogenic differentiation. Mechanically, miR-193a targeted and negative regulated SIRT7. Additionally, it was confirmed that SIRT7 promoted osteogenic differentiation of BMSCs through NF-κB signaling pathway. Further study indicated that RES exerted its beneficial function through miR-193a/SIRT7-mediated NF-κB signaling to alleviate osteoporosis in vivo. Our research suggested that the RES-modulated miR-193a inhibition is responsible for the activation of SIRT7/NF-κB signaling pathway in the process of osteogenic differentiation, providing a novel insight into diagnosis and treatment of osteoporosis.

[Total knee arthroplasty for the treatment of hemophilic arthropathy of the knee].

OBJECTIVE: To study the efficacy of total knee anhmplasty (TKA) for the treatment of hemophilic knee arthropathy, and to explore the operative characteristics, the selection of prothesis, the effectiveness and safety of clotting factor replacement treatment. METHODS: From January 2008 to June 2010, 10 patients (12 knees)with hemophilic anhropathv underwent TKA. The average age was 33.6 years old (ranged, 17 to 49 years). There was 8 cases of type A hemophilia and 2 cases of type B hemophilia. According to Arnold and Hilgartner classification: 7 knees were IV degree and 5 knees were V degree. The level of VIII factor for replacement treatment was more than 80% on operation day, more than 60% within 3 days after operation, more than 40% from the third day to the second week after operation. Added prothrombin complex concentrate (PCC) to improve the level of IX factor, and the level of IX factor for replacement treatment was more than 40% on operation day, more than 30% within 3 days after operation, more than 20% from the third day to the second week after operation. Functional training was mainly based on continuous passive motion (CPM) device after surgery. Clinical assessment included hospital for special surgery knee score (HSS) and the individual scores (including pain, function, activity, muscle strength, flexion deformity and stability). RESULTS: Ten patients (12 knees) were followed-up, and the average duration was 11 months (ranged, 6 to 24 months). The average preoperative HSS score was (44.9 +/- 12.5) (ranged, 29 to 62 scores), whereas the average postoperative HSS score was (84.4 +/- 10.2) (ranged 72 to 96 scores) (P < 0.01). The preoperative individual score including pain, function, activity, muscle strength flexion deformity and stability were significantly improved compared with pre-operation, the differences between them were statistically significant (P < 0.01 ). TKA had the distinct role in relieving pain from preoperative (8.5 +/- 4.1) to postoperative (24.5 +/- 4.4). CONCLUSION: Under the strict perioperative coagulation factor replacement therapy, TKA is a safe and an effective treatment for hemophmc anhmpathy of knee joint, whicht can effectively relieve pain and improve joint function.