Dataset Information

MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression.

ABSTRACT: Distraction osteogenesis (DO) is a unique technique for promoting bone formation in clinical practice. However the underlying mechanism remains elusive. As epigenetic mediators, microRNAs have been reported to play important roles in regulating osteogenesis. In this study, after successfully established the DO model of rats, a microRNA microarray was performed to find molecular targets for DO. Total 100 microRNAs were identified as differently expressed, with miR-503 being one of the most significantly up-regulated miRNAs in DO. The further investigation also showed that miR-503 was upregulated during osteogenesis in mesenchymal stem cells of rats, and overexpression of miR-503 significantly promoted osteogenesis in vitro and accelerated mineralization in DO process in vivo. By using bioinformatic investigations and luciferase activities, we successfully demonstrated that Smurf1, a negative regulator of osteogenesis, was a real target of miR-503. Furthermore, Smurf1 knockdown promoted osteogenesis and antagomir-503 abolished the promotive effect, suggesting that miR-503 mediated osteogenic differentiation via suppressing Smurf1 expression. To sum up, these findings indicated that miR-503 promoted osteogenesis and accelerated bone formation, which may shed light on the development for a potential therapeutic target for bone repair.

SUBMITTER: Sun Y

PROVIDER: S-EPMC5428455 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression.

Sun Yuxin Y Xu Jia J Xu Liangliang L Zhang Jinfang J Chan Kaiming K Pan Xiaohua X Li Gang G

Scientific reports 20170324 1

Distraction osteogenesis (DO) is a unique technique for promoting bone formation in clinical practice. However the underlying mechanism remains elusive. As epigenetic mediators, microRNAs have been reported to play important roles in regulating osteogenesis. In this study, after successfully established the DO model of rats, a microRNA microarray was performed to find molecular targets for DO. Total 100 microRNAs were identified as differently expressed, with miR-503 being one of the most signif ...[more]

PMID: 28341855

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Project description:Background: Interfragmentary movements have benefits in the improvement of bone formation during distraction osteogenesis (DO). Although several clinical studies reported positive outcomes regarding the application of the cyclic distraction-compression (CDC) dynamization technique in cases with poor bone formation during DO, they are mostly anecdotal without a detailed description. The purpose of this study was to investigate the effectiveness and potential mechanism of different amplitudes and rates of the CDC technique on bone regeneration in a rat femur DO model. Methods: A total of 60 adult male Sprague-Dawley rats underwent right femoral mid-diaphysis transverse osteotomy and were randomly and evenly divided into Control (no manipulation), Group1 (CDC therapy), Group2 (CDC therapy with larger amplitude), and Group3 (CDC therapy with a slower rate) after distraction. The CDC technique was performed during the middle phase of the consolidation period according to different protocols. Animals were sacrificed after 4 and 6 weeks of consolidation. The process of bone formation was monitored by digital radiographs, and the regenerate bone was evaluated by micro-computed tomography (micro-CT), biomechanical test, and histological analysis. The serum contents of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay (ELISA). Results: Bone regeneration after the CDC technique was improved significantly during DO. The digital radiograph, micro-CT, histomorphological analysis, and biomechanical evaluation showed better effects regarding volume, continuity, and mechanical properties of the regenerate bone in Group2 and Group3 when compared to Group1. The angiogenic and osteogenic markers were more highly expressed in Group2 and Group3 than in Group1 according to the immunohistochemical analysis. As for ELISA, the serum contents of HIF-1α and VEGF were also increased after the CDC technique, especially in Group2 and Group3. Conclusion: The CDC dynamization technique has benefits on the improvement of bone formation during DO, and the mechanism may be due to tissue hypoxia activating the HIF pathway followed by the augmentation of osteogenic-angiogenic coupling. Better outcomes may be achieved by moderately increasing the amplitude and slowing down the rate of the CDC technique.

Project description:BackgroundHypoxia is the critical driving force for angiogenesis and can trigger the osteogenic-angiogenic coupling followed by the enhancement of bone regeneration. While lots of studies showed that hypoxia administration can accelerate bone formation during distraction osteogenesis (DO), the therapeutic timing for the osteogenic purpose was concentrated on the distraction phase. The outcomes of hypoxia administration in the consolidation phase stay uncertain. The purpose of this study was to determine the osteogenic effectiveness of hypoxia therapy during the consolidation phase, if any, to enhance bone regeneration in a rat femoral DO model.MethodsA total of 42 adult male Sprague-Dawley rats underwent right femoral mid-diaphysis transverse osteotomy and were randomly divided into Control (NS administration, n = 21) and Group1 (deferoxamine therapy, n = 21) after distraction. During the consolidation phase, Group1 was treated with local deferoxamine (DFO) injection into the distraction zone, while the Control underwent the same dosage of NS. Animals were sacrificed after 2, 4, and 6 weeks of consolidation. The process of bone formation and remodeling was monitored by digital radiographs, and the regenerated bone was evaluated by micro-computed tomography (micro-CT), biomechanical test, and histological analysis. The serum content of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by enzyme linked immunosorbent assay (ELISA) for further analysis.ResultsBone regeneration was significantly enhanced after hypoxia therapy during the consolidation phase. The digital radiograph, micro-CT, and biomechanical evaluation showed better effects regarding volume, continuity, and mechanical properties of the regenerated bone in Group1. The histomorphological evaluation also revealed the hypoxia treatment contributed to accelerate bone formation and remodeling during DO. The higher positive expression of angiogenic and osteogenic markers were observed in Group1 after hypoxia administration according to the immunohistochemical analysis. The serum content of HIF-1α and VEGF was also increased after hypoxia therapy as evidenced from ELISA.ConclusionHypoxia administration during the consolidation phase of distraction osteogenesis has benefits in enhancing bone regeneration, including accelerates the bone formation and remodeling.

Dataset Information

MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression.

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MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression.

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