Department of Orthopaedics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, People's Republic of China.
Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, People's Republic of China.
Cell Biol Int. 2019 May;43(5):565-573. doi: 10.1002/cbin.11133. Epub 2019 Apr 25.
Heterotopic ossification (HO) is a common disturbing complication of intra-articular fractures. Its prevention and treatment are still difficult as its pathogenesis is unclear. It was reported that PDGFRα muscle cells in skeletal muscle may participate in the formation of HO; however, the specific mechanism is still unknown. This study investigated the function of miR-19b-3p in osteogenic differentiation of PDGFRα muscle cells. MiR-19b-3p was upregulated during PDGFRα muscle cell osteogenic differentiation. The exogenous expression of miR-19b-3p led to an increase in osteogenic marker gene transcription and translation during the osteogenic differentiation of PDGFRα muscle cells. Furthermore, both alkaline phosphatase and alizarin red staining increased in miR-19b-3p mimic transfected cells. Over-expression of miR-19b-3p led to the down-regulation of gene of phosphate and tension homology deleted on chromosome ten (PTEN). Additionally, the dual luciferase reporter assay demonstrated that PTEN was a direct target of miR-19b-3p. The increase of osteocalcin, osteopontin, and Runt-related transcription factor 2 protein levels induced by ectopic miR-19b-3p expression could be partially reversed by PTEN over-expression. In conclusion, our results suggested that miR-19b-3p may be a promising target in inhibiting PDGFRα muscle cell osteogenic differentiation and treatment of HO.
异位骨化 (HO) 是关节内骨折的一种常见并发症，其发病机制尚不清楚，因此预防和治疗仍然困难。有报道称，骨骼肌中的 PDGFRα 肌细胞可能参与 HO 的形成，但具体机制尚不清楚。本研究探讨了 miR-19b-3p 在 PDGFRα 肌细胞成骨分化中的作用。miR-19b-3p 在 PDGFRα 肌细胞成骨分化过程中上调。外源性表达 miR-19b-3p 导致 PDGFRα 肌细胞成骨分化过程中骨形成标志物基因的转录和翻译增加。此外，碱性磷酸酶和茜素红染色均增加了 miR-19b-3p 模拟物转染细胞。miR-19b-3p 的过表达导致了第十号染色体缺失的磷酸和张力同源物 (PTEN) 基因的下调。此外，双荧光素酶报告基因实验表明，PTEN 是 miR-19b-3p 的直接靶基因。外源性 miR-19b-3p 表达诱导的骨钙素、骨桥蛋白和 runt 相关转录因子 2 蛋白水平的增加可以部分被过表达的 PTEN 逆转。总之，我们的研究结果表明，miR-19b-3p 可能是抑制 PDGFRα 肌细胞成骨分化和治疗 HO 的有前途的靶点。
