Rapid and extensive bone loss, one of the skeletal complications after spinal cord injury (SCI) occurrence, drastically sacrifices the life quality of SCI patients. It has been demonstrated that microRNA (miRNA) dysfunction plays an important role in the initiation and development of bone loss post‐SCI. Nevertheless, the effect of miR‐19b‐3p on bone loss after SCI is unknown and the accurate mechanism is left to be elucidated. The present work was conducted to explore the role of miR‐19b‐3p/phosphatase and tensin homolog deleted on chromosome ten (PTEN) axis on osteogenesis after SCI and further investigates the underlying mechanisms. We found that miR‐19b‐3p level was increased in the femurs of SCI rats with decreased autophagy. The overexpression of miR‐19b‐3p in bone marrow mesenchymal stem cells (BMSCs) targeted down‐regulation of PTEN expression, facilitated protein kinase B (Akt) and mammalian target of rapamycin (mTOR) phosphorylation, and thereby suppressing BMSCs osteogenic differentiation via autophagy. Besides, the inhibiting effects of miR‐19b‐3p on osteogenic differentiation of BMSCs could be diminished by autophagy inducer rapamycin. Meanwhile, bone loss after SCI in rats was also reversed by antagomir‐19b‐3p treatment, suggesting miR‐19b‐3p was an essential target for osteogenic differentiation via regulating autophagy. These results indicated that miR‐19b‐3p was involved in bone loss after SCI by inhibiting osteogenesis via PTEN/Akt/mTOR signalling pathway.

中文翻译：

---

MiR-19b-3p 通过调节 PTEN/Akt/mTOR 信号传导抑制成骨，加速脊髓损伤后骨质流失


快速而广泛的骨质流失是脊髓损伤（SCI）发生后的骨骼并发症之一，极大地牺牲了SCI患者的生活质量。已证明 microRNA (miRNA) 功能障碍在 SCI 后骨质流失的发生和发展中发挥着重要作用。然而，miR-19b-3p 对 SCI 后骨丢失的影响尚不清楚，其准确机制有待阐明。本工作旨在探讨十号染色体（PTEN）轴上缺失的 miR-19b-3p/磷酸酶和张力蛋白同源物对 SCI 后成骨的作用，并进一步研究其潜在机制。我们发现自噬降低的 SCI 大鼠股骨中 miR-19b-3p 水平升高。骨髓间充质干细胞（BMSCs）中miR-19b-3p的过表达靶向下调PTEN表达，促进蛋白激酶B（Akt）和哺乳动物雷帕霉素靶点（mTOR）磷酸化，从而通过自噬抑制BMSCs成骨分化。此外，自噬诱导剂雷帕霉素可以减弱miR-19b-3p对BMSCs成骨分化的抑制作用。同时，大鼠 SCI 后的骨质流失也可通过 antagomir-19b-3p 治疗逆转，这表明 miR-19b-3p 是通过调节自噬进行成骨分化的重要靶标。这些结果表明，miR-19b-3p 通过 PTEN/Akt/mTOR 信号通路抑制成骨，从而参与 SCI 后的骨丢失。