MiR-19b-3p下调PTEN促进PDGFRα+细胞成骨分化在获得性异位骨化中的作用和机制研究

Heterotopic ossification (HO) is a common complication of trauma, and affect joint function frequently. Its prevention and treatment are still very difficult as its pathogenesis is unclear. It was reported that PDGFRα+ cells in skeletal muscle may participated in the formation of HO, however the specific mechanisms are unknown. Our previous study have found that miR-19b-3p can promote PDGFRα+ cells osteogenic differentiation for the first time. Further studies indicated that PTEN was one of the target genes of miR-19b-3p. In this study, the possible molecular mechanisms of miR-19b-3p promotes PDGFRα+ cells osteogenic differentiation in HO formation will be explored ; The serum miR-19b-3p concentration of different patients will be detected and compared; Furthermore, we will investigate the inhibiting effect of antagomiR-19b-3p on bone formation in mice. The study will provide a new molecular target for HO diagnosis and prevention.

异位骨化（HO）是创伤患者的常见并发症，常导致关节功能障碍，发病机制至今不明，其防治仍非常棘手。文献报道骨骼肌PDGFRα+细胞参与了HO的形成，但具体机制不详。我们前期研究首次发现miR-19b-3p对PDGFRα+细胞成骨分化具有促进作用；进一步的生物信息学分析和细胞实验证明PTEN为miR-19b-3p的靶基因。本课题拟阐明miR-19b-3p促进PDGFRα+细胞成骨分化和HO形成的分子机制；检测和比较不同HO风险组别以及各组HO患者和非HO患者的血清miR-19b-3p含量是否有差别；通过小鼠HO模型内注射antagomiR-19b-3p，观察可否抑制HO形成。本课题的完成将为HO的预防和早期诊断开辟新的思路。

异位骨化（HO）是创伤患者的常见并发症，常导致关节功能障碍，发病机制至今不明，其防治仍非常棘手。文献报道骨骼肌PDGFRα+细胞参与了HO的形成，但具体机制不详。我们前期研究首次发现miR-19b-3p对PDGFRα+细胞成骨分化具有促进作用；进一步的生物信息学分析和细胞实验证明PTEN为miR-19b-3p的靶基因。本课题构建了小鼠HO模型，结果表明miR-19b-3p和PTEN在HO中的表达呈负相关。miR-19b-3p mimics组的HO形成显著高于其他组，而PTEN的表达也显著降低。局部注射antagomiR-19b-3p可抑制HO的形成。我们的研究结果表明MiR-19b-3p通过下调PTEN促进PDGFRα+细胞成骨分化从而促进获得性HO的形成。本课题的完成将为HO的预防和早期诊断开辟新的思路。