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 β-catenin expression in MEG3 knockdown BMSCs. Dickkopf 1 (DKK1) was used to block wnt/β-catenin pathway. The osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs after wnt/β-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/β-catenin signaling pathway in BMSCs. Wnt/β-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.
Background: Previous studies have demonstrated long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. However, whether MEG3 participate in osteogenic differentiation and bone regeneration remains unclear. 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 were detected by qPCR. MEG3 was knockdown in BMSCs by lentivirus. The proliferation, osteogenic-related genes and proteins expression were assessed by the CCK-8, PCR, alizarin red and alkaline phosphatase staining in MEG3 knockdown BMSCs. Western blot was used to detected β-catenin expression in MEG3 knockdown BMSCs. DKK1 was used to block wnt/β-catenin pathway, the osteogenic-related genes and proteins expression were assessed by PCR, alizarin red and alkaline phosphatase staining in MEG3 knockdown BMSCs. MEG3 knockdown BMSCs scaffold with PHMG were implanted in a critical-sized skull defects of rat model, micro-CT, hematoxylin and eosin staining, and immunohistochemistry were performed to evaluate the bone repairing. Results: 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 MEG3 knockdown could activate Wnt/β-catenin signaling pathway in BMSCs. Wnt/β-catenin inhibition would impair MEG3-induced osteogenic differentiation of BMSCs. By using PHMG scaffold with MEG3 knockdown BMSCs, we found that downregulation of MEG3 in BMSCs could accelerated 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.
Background. Hip fracture is a common occurrence in elderly populations and is frequently followed by various levels of cognitive dysfunction, leading to adverse functional outcomes. Risk stratification of hip fracture patients to identify high-risk subsets can enable improved strategies to mitigate cognitive complications. The neuropeptide galanin has multiple neurological functions, and altered levels are documented in dementia-type and depression disorders. The present study investigated the association of serum neuropeptide galanin levels in hip fracture patients with the occurrence of cognitive dysfunction during the first week of admission. Methods. 276 hip fracture patients without preexisting delirium, cognitive impairment, or severe mental disorders were included in a cross-sectional study. Serum galanin levels were assessed by ELISA on the second day of admission. Routine clinical and laboratory variables were documented. MoCA was performed within 1 week, and those with a score < 26 were categorized with “cognitive decline.” Inferential statistics including multiple linear regression analysis were applied to determine the association of serum galanin level and cognitive status. Results. 141 patients were categorized with “cognitive decline,” and 135 patients were categorized as “cognitively normal.” Serum galanin was highly significantly increased in the “cognitive decline” group ( 34.2 ± 4.8 , pg/ml) compared to the “cognitively normal” group ( 28.9 ± 3.7 , pg/ml) and showed significant negative correlation with MoCA scores ( r = − 0.229 , p = 0.016 ). Regression analysis showed serum galanin as the sole significant independent predictor of lower MoCA scores ( β = 0.231 , p = 0.035 ) while age, gender, blood pressure, cholesterol, and blood glucose levels had no significant association. Conclusion. Higher serum galanin predicted the development of cognitive dysfunction and worse MoCA scores in a cohort of hip fracture patients without preexisting cognitive impairment or delirium at admission, thus warranting large-scale studies investigating galanin as a candidate biomarker to identify hip fracture patients at risk of cognitive decline.
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