RESUMO
BACKGROUND: Previous studies have demonstrated that long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. This study aims to investigate the function and mechanism of MEG3 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explores the use of MEG3 in skull defects bone repairing. METHODS: Endogenous expression of MEG3 during BMSCs osteogenic differentiation was detected by quantitative real-time polymerase chain reaction (qPCR). MEG3 was knockdown in BMSCs by lentiviral transduction. The proliferation, osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs were assessed by Cell Counting Kit-8 (CCK-8) assay, qPCR, alizarin red and alkaline phosphatase staining. Western blot was used to detect ß-catenin expression in MEG3 knockdown BMSCs. Dickkopf 1 (DKK1) was used to block wnt/ß-catenin pathway. The osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs after wnt/ß-catenin inhibition were assessed by qPCR, alizarin red and alkaline phosphatase staining. MEG3 knockdown BMSCs scaffold with PHMG were implanted in a critical-sized skull defects of rat model. Micro-computed tomography(micro-CT), hematoxylin and eosin staining and immunohistochemistry were performed to evaluate the bone repairing. RESULTS: Endogenous expression of MEG3 was increased during osteogenic differentiation of BMSCs. Downregulation of MEG3 could promote osteogenic differentiation of BMSCs in vitro. Notably, a further mechanism study revealed that MEG3 knockdown could activate Wnt/ß-catenin signaling pathway in BMSCs. Wnt/ß-catenin inhibition would impair MEG3-induced osteogenic differentiation of BMSCs. By using poly (3-hydroxybutyrate-co-3-hydroxyhexanoate, PHBHHx)-mesoporous bioactive glass (PHMG) scaffold with MEG3 knockdown BMSCs, we found that downregulation of MEG3 in BMSCs could accelerate bone repairing in a critical-sized skull defects rat model. CONCLUSIONS: Our study reveals the important role of MEG3 during osteogenic differentiation and bone regeneration. Thus, MEG3 engineered BMSCs may be effective potential therapeutic targets for skull defects.
RESUMO
Ideberg type III glenoid fractures with associated superior shoulder suspensory complex (SSSC) injuries are rare, and related treatments have not been reported in the literature. The purpose of this study was to evaluate the clinical outcomes of such injuries treated with open reduction and internal fixation (ORIF). Between July 2007 and April 2012, ten patients with Ideberg type III glenoid fractures were surgically treated using ORIF with 2 cannulated screws or a screw combined with a metacarpal plate through an anterior approach. Patients with associated SSSC injuries underwent ORIF with K-wires or plates. Information was available for 9 patients with a mean follow-up of 24.1±18.2 months. Mean bone-healing time was 8.4±2.2 weeks. At last follow-up, mean forward flexion of the operative shoulder was 157.8°±7.5°, mean external rotation was 62.9°±7.9°, and mean internal rotation was thoracic level T6±0.8. Mean Constant score was 84.1±3.7 points, which was a mean of 92.7%±3.4% of that seen in the contralateral shoulder. Mean UCLA score and Disabilities of the Arm, Shoulder and Hand score were 33.6±1.7 and 16.6±7.7, respectively. The results show that Ideberg type III glenoid fractures with associated SSSC injuries can be successfully treated using ORIF through an anterior approach. Glenoid fractures and SCCC injuries should be treated simultaneously.