Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
J Cell Mol Med. 2021 Jan;25(2):990-1000. doi: 10.1111/jcmm.16159. Epub 2020 Dec 17.
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.
脊髓损伤(SCI)发生后,迅速广泛的骨丢失是骨骼并发症之一,极大地降低了 SCI 患者的生活质量。已经证明,微小 RNA(miRNA)功能障碍在 SCI 后骨丢失的发生和发展中起重要作用。然而,miR-19b-3p 对 SCI 后骨丢失的影响尚不清楚,其确切机制仍有待阐明。本研究旨在探讨 miR-19b-3p/磷酸酶和张力蛋白同源物缺失的染色体 10(PTEN)轴在 SCI 后成骨中的作用,并进一步探讨其潜在机制。我们发现,SCI 大鼠股骨中 miR-19b-3p 水平升高,自噬减少。miR-19b-3p 在骨髓间充质干细胞(BMSCs)中的过表达靶向下调 PTEN 表达,促进蛋白激酶 B(Akt)和哺乳动物雷帕霉素靶蛋白(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,抗 miR-19b-3p 处理也逆转了大鼠 SCI 后的骨丢失,表明 miR-19b-3p 通过调节自噬来调节成骨分化是必不可少的。这些结果表明,miR-19b-3p 通过 PTEN/Akt/mTOR 信号通路抑制成骨作用参与 SCI 后的骨丢失。