CHI3L1 regulation of inflammation and the effects on osteogenesis in a Staphylococcus aureus-induced murine model of osteomyelitis
CHI3L1 regulation of inflammation and the effects on osteogenesis in a Staphylococcus aureus-induced murine model of osteomyelitis
复制标题
CHI3L1 对金黄色葡萄球菌诱导的小鼠骨髓炎模型中炎症的调节及其对成骨的影响
DOI：
10.1111/febs.14082
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发表时间：
2017-06-01
期刊：
影响因子：
5.4
通讯作者：
Jin, Tao
中科院分区：
文献类型：
--
作者：
Chen, XueQiu;Jiao, Jian;Jin, Tao
骨髓炎是一种骨骼和骨髓的炎症，主要是由金黄色葡萄球菌感染引起的。在之前的研究中，我们发现几丁质酶3样1 （CHI3L1）基因的表达影响金黄色葡萄球菌感染的MC3T3-E1细胞的矿化，骨髓炎患者血液中CHI3L1的表达增加。在本研究中，为了进一步研究CHI3L1在骨髓炎中的作用，我们建立了金黄色葡萄球菌诱导的骨髓炎小鼠模型。我们发现，与接种PBS对照的小鼠相比，感染金黄色葡萄球菌的小鼠股骨中CHI3L1的表达显著上调。为了进一步研究这些结果，我们通过慢病毒介导的RNA干扰在小鼠中进行了CHI3L1敲除。感染股骨的显微计算机断层扫描显示，金黄色葡萄球菌引发骨转换的深刻改变，与感染金黄色葡萄球菌的对照组小鼠相比，注射CHI3L1短发夹RNA （shRNA-CHI3L1）的小鼠感染金黄色葡萄球菌后，其股骨皮质骨破坏明显减少。抑制CHI3L1还通过降低促炎细胞因子水平来减轻炎症，促进成骨过程。Notch信号通路已被证明在调节成骨细胞和破骨细胞的分化中发挥重要作用。我们的研究表明，与对照组相比，金黄色葡萄球菌感染小鼠的Notch1、Jagged1和Hes1的表达明显降低，而shRNA-CHI3L1可以提高金黄色葡萄球菌感染小鼠的Notch1、Jagged1和Hes1的表达。本研究表明，抑制CHI3L1可以减少金黄色葡萄球菌在小鼠骨髓炎模型中的衰弱作用。
Osteomyelitis is an inflammation of the bone and bone marrow that occurs as a consequence of infections mainly attributed to Staphylococcus aureus. In a previous study, we found that expression of the chitinase 3-like 1 (CHI3L1) gene affected mineralization of MC3T3-E1 cells infected with S. aureus and there was increased expression of CHI3L1 in the blood of osteomyelitis patients. In the present study, to further investigate the role of CHI3L1 in osteomyelitis, we developed an S. aureus-induced murine model of the disease. We found that the expression of CHI3L1 was significantly up-regulated in femurs of mice infected with S. aureus compared with mice inoculated with a PBS control. To investigate these results further, we performed a CHI3L1 knock-down by lentivirus-mediated RNA interference in mice. Micro-computed tomography of infected femurs revealed that S. aureus triggers profound alterations in bone turnover, and femurs of CHI3L1 short hairpin RNA (shRNA-CHI3L1)-injected mice infected with S. aureus have significantly less cortical bone destruction when compared with control mice infected with S. aureus. Inhibition of CHI3L1 also decreased inflammation by reducing levels of proinflammatory cytokines and promoted the process of osteogenesis. The Notch signaling pathway has been shown to play an important role in modulating the differentiation of osteoblasts and osteoclasts. Our study showed that Notch1, Jagged1 and Hes1 expression significantly decreased in mice infected with S. aureus compared with the control, and shRNA-CHI3L1 could increase their level in S. aureus-infected mice. This research indicates that inhibition of CHI3L1 can reduce the debilitating effects of S. aureus in a murine model of osteomyelitis.