Department of Orthopedics, Wuxi People's Hospital, Wuxi, China.
J Orthop Res. 2012 Nov;30(11):1837-42. doi: 10.1002/jor.22128. Epub 2012 Apr 16.
Previous studies have found that microRNA-21 (miR-21) is an important functional factor during osteoclast differentiation. Abnormal osteoclastogenesis induced by wear particles is the main cause of aseptic loosening in joint replacements. The aim of the present study is to investigate the possible role of miR-21 in the pathogenesis of particle-induced osteolysis (PIO). miR-21 expression was examined in a PIO mouse model using real-time (RT-PCR). Osteoclastogenesis was determined by a tartrate resistant acid phosphatase (TRAP) quantification method. A toluidine blue staining assay was used to examine calvarial osteolysis. The results demonstrated that miR-21 was significantly upregulated in the PIO animal model. Knocking out miR-21 in the particle-stimulated tissue could ameliorate osteolysis symptoms. Additionally, through our analysis of PDCD4 and AP-1 expression, we suggest that the feedback loop of AP-1, miR-21, and PDCD4 might have an important influence on the development of PIO and that miR-21 is a potential target for implant loosening therapies.
先前的研究发现,microRNA-21(miR-21)是破骨细胞分化过程中的一个重要功能因子。磨损颗粒诱导的破骨细胞异常生成是关节置换术后无菌性松动的主要原因。本研究旨在探讨 miR-21 在颗粒诱导性骨溶解(PIO)发病机制中的可能作用。采用实时(RT-PCR)检测 PIO 小鼠模型中 miR-21 的表达。通过抗酒石酸酸性磷酸酶(TRAP)定量法测定破骨细胞生成。采用甲苯胺蓝染色法检测颅骨骨溶解。结果表明,miR-21 在 PIO 动物模型中显著上调。在颗粒刺激的组织中敲除 miR-21 可以改善骨溶解症状。此外,通过对 PDCD4 和 AP-1 表达的分析,我们认为 AP-1、miR-21 和 PDCD4 的反馈环可能对 PIO 的发展有重要影响,并且 miR-21 是植入物松动治疗的潜在靶点。