Jin Tao, Lu Yong, He Qing Xiao, Wang Hai, Li Bing Fu, Zhu Liang Yue, Xu Qing Yong
Department of Orthopedic Surgery, Kunming General Hospital Chengdu Military Command, Kunming, 650032, PR China.
Department of Radiology, School of Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, 200025, PR China.
J Cell Biochem. 2015 Dec;116(12):2804-13. doi: 10.1002/jcb.25225.
Osteomyelitis is a debilitating infectious disease of the bone which is predominantly caused by Staphylococcus aureus (S. aureus). MicroRNAs (miRNAs) have been shown to play a regulatory role in osteogenesis. In the present study, the expression levels of miRNAs proposed to potentially play a regulatory role in bone formation or differentiation (miR-24, miR-29b, miR-200a, miR-208, miR-322) were analyzed in the whole blood of patients with bacterial osteomyelitis or healthy controls, and in MC3T3-E1 cells infected with S. aureus by qRT-PCR. The expression of miR-24 was significantly down-regulated in osteomyelitis patients and S. aureus-infected MC3T3-E1 cells compared with the healthy controls or untreated control cells. Moreover, our results showed that S. aureus inhibited MC3T3-E1 cell proliferation, induced osteoblast apoptosis and prohibited bone formation and mineralization. We found that overexpression of miR-24 could reduce the effects of S. aureus, while inhibition of miR-24 intensified the effects. We also demonstrated that miR-24 suppressed the expression of chitinase 3-like 1 (CHI3L1) mRNA, thought to mediate multiple signaling pathways, by directly binding to the 3'-untranslated region.
骨髓炎是一种使人衰弱的骨感染性疾病,主要由金黄色葡萄球菌(金葡菌)引起。微小RNA(miRNA)已被证明在骨生成中起调节作用。在本研究中,通过qRT-PCR分析了拟在骨形成或分化中可能起调节作用的miRNA(miR-24、miR-29b、miR-200a、miR-208、miR-322)在细菌性骨髓炎患者或健康对照者的全血中以及在感染金葡菌的MC3T3-E1细胞中的表达水平。与健康对照者或未处理的对照细胞相比,miR-24在骨髓炎患者和感染金葡菌的MC3T3-E1细胞中的表达显著下调。此外,我们的结果表明,金葡菌抑制MC3T3-E1细胞增殖,诱导成骨细胞凋亡,并抑制骨形成和矿化。我们发现,miR-24的过表达可减轻金葡菌的作用,而抑制miR-24则会增强其作用。我们还证明,miR-24通过直接结合3'-非翻译区来抑制几丁质酶3样1(CHI3L1)mRNA的表达,CHI3L1被认为可介导多种信号通路。