Staphylococcus Aureus Induces Osteoclastogenesis via the NF-κB Signaling Pathway.
Staphylococcus Aureus Induces Osteoclastogenesis via the NF-κB Signaling Pathway.
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金黄色葡萄球菌通过 NF-kappa B 信号通路诱导破骨细胞生成
DOI：
10.12659/msm.903371
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发表时间：
2017-09-24
期刊：
影响因子：
--
通讯作者：
Xu YQ
中科院分区：
文献类型：
--
作者：
Ren LR;Wang ZH;Wang H;He XQ;Song MG;Xu YQ
骨髓炎是骨科遇到的难治性疾病之一，而金黄色葡萄球菌（S. aureus）是骨髓炎最常见的致病菌。然而，金黄色葡萄球菌感染导致骨质流失的确切机制尚未明确。本文研究了金黄色葡萄球菌对破骨细胞分化的影响及其可能的分子机制。用活的金黄色葡萄球菌、灭活的金黄色葡萄球菌和金黄色葡萄球菌滤液处理RAW 264.7细胞5天。然后观察破骨细胞样细胞的形成和吸收坑的形成，并通过实时荧光定量PCR检测破骨细胞特异性基因（TRAP、MMP-9、cathepsin K、CTR和Atp6v0d2）的表达。Western blot检测破骨细胞分化信号通路中的关键蛋白。数据显示，在缺乏RANKL的情况下，活的金黄色葡萄球菌、灭活的金黄色葡萄球菌和金黄色葡萄球菌滤液诱导破骨细胞形成，促进骨吸收，并以剂量依赖的方式增加破骨细胞特异性基因的表达。此外，我们发现金黄色葡萄球菌诱导的破骨细胞发生与i -κB -α降解、NF-κB p65磷酸化、NFATc1表达升高有关。因此，我们使用JSH-23抑制NF-κB的转录活性。金黄色葡萄球菌诱导的破骨细胞生成及破骨细胞特异性基因和NFATc1的表达均受到抑制，提示NF-κB信号通路在金黄色葡萄球菌诱导的破骨细胞生成中发挥作用。本研究表明，金黄色葡萄球菌通过其细胞壁化合物和可溶性小分子的分泌诱导破骨细胞发生，而NF-κB信号通路在这一过程中起作用。
Osteomyelitis is one of the refractory diseases encountered in orthopedics, while Staphylococcus aureus (S. aureus) is the most common causative organism in osteomyelitis. However, the precise mechanisms underlying the bone loss caused by S. aureus infection have not been well defined. Here, we investigated the effect of S. aureus on osteoclast differentiation and the probable molecular mechanism. RAW 264.7 cells were treated for 5 days with live S. aureus, inactivated S. aureus, and S. aureus filtrate. Then, the formation of osteoclast-like cells and resorption pits was observed, and the expression of osteoclast-specific genes (TRAP, MMP-9, cathepsin K, CTR and Atp6v0d2) was detected by real-time PCR. Moreover, key proteins in the signaling pathway associated with osteoclast differentiation were detected with Western blot. The data showed that live S. aureus, inactivated S. aureus, and S. aureus filtrate induced osteoclast formation, promoted bone resorption, and increased the expression of osteoclast-specific genes in a dose-dependent manner in the absence RANKL. In addition, we found that the S. aureus-induced osteoclastogenesis was related to the degradation of IκB-α, phosphorylation of NF-κB p65, and increased expression of NFATc1. Thus, we used JSH-23 to inhibit NF-κB transcriptional activity. The effect of the S. aureus-induced osteoclastogenesis and the expression of osteoclast-specific genes and NFATc1 were inhibited, which indicated that the NF-κB signaling pathway plays a role in S. aureus-induced osteoclastogenesis. This study demonstrated that S. aureus induces osteoclastogenesis through its cell wall compound and secretion of small soluble molecules, and the NF-κB signaling pathway plays a role in this process.
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DOI：
10.1084/jem.190.12.1741
发表时间：
1999-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Arai F;Miyamoto T;Ohneda O;Inada T;Sudo T;Brasel K;Miyata T;Anderson DM;Suda T
通讯作者：
Suda T
影响因子：
3.7
作者：
Grimbly C;Odenbach J;Vandermeer B;Forgie S;Curtis S
通讯作者：
Curtis S
影响因子：
2.3
作者：
Labbe, J. -L.;Peres, O.;Lacassin, F.
通讯作者：
Lacassin, F.
影响因子：
15.3
作者：
Asagiri, M;Sato, K;Takayanagi, H
通讯作者：
Takayanagi, H
巨噬细胞刺激因子刺激分离的破骨细胞中的存活和趋化行为。
DOI：
10.1084/jem.178.5.1733
发表时间：
1993-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fuller K;Owens JM;Jagger CJ;Wilson A;Moss R;Chambers TJ
通讯作者：
Chambers TJ