确定巨噬细胞和 γδ-T 细胞促进唑来膦酸相关性颌骨坏死的分子机制。
Determination of the molecular mechanism by which macrophages and γδ-T cells contribute to ZOL-induced ONJ.
机构信息
Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiaotong University, School of Medicine, Shanghai, 200011, China.
Department of Orthopedics, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200336, China.
出版信息
Aging (Albany NY). 2020 Oct 25;12(20):20743-20752. doi: 10.18632/aging.104006.
OBJECTIVE
This study aims to explore the molecular mechanism of macrophages and γδ-T cells in the ZOL drug-induced osteonecrosis of jaws based on the IFN-γ involved osteoblast differentiation signaling pathway.
RESULTS
The number and apoptotic rate of CD11b+Gr1hi cells and γδ-T cells in the ONJ group were significantly higher. The TNF-α, IL-1β, IFN-γ, CCL3, CCL4, IL-12 and IL-13 levels were significantly higher in the ONJ group. The expression of CTSK and FGFR3 was lower in the ONJ group, but was higher in the NF-κB and ERBB2IP group.
CONCLUSION
The proliferation of macrophages and γδ-T cells promote the inflammation in ZOL-induced jaw necrosis.
METHODS
A total of 20 patients with osteonecrosis of the jaw from January 2016 to March 2018 were collected and assigned into the observation group, while 20 healthy subjects were assigned into the control group. Furthermore, 40 SD rats were selected and assigned into observation group, while 10 non-treatment SD rats were selected and assigned as controls. The distribution and proportion of CD11b+Gr1hi cells and γδ-T cells in the necrotic tissues of the jaw were analyzed. Then, the TNF-α, IL-1β, IFN-γ, CCL3, CCL4, IL-12 and IL-13 levels were measured. Afterwards, the expression of CTSK, FGFR3, NF-κB and ERBB2IP in the necrotic tissues of the jaw in the animal models were analyzed.
目的
本研究旨在探讨干扰素-γ（IFN-γ）参与破骨细胞分化信号通路在唑来膦酸（ZOL）药物诱导颌骨坏死中巨噬细胞和γδ-T 细胞的分子机制。
结果
ONJ 组 CD11b+Gr1hi 细胞和 γδ-T 细胞数量及凋亡率显著升高，TNF-α、IL-1β、IFN-γ、CCL3、CCL4、IL-12、IL-13 水平显著升高，ONJ 组 CTSK、FGFR3 表达水平较低，NF-κB、ERBB2IP 表达水平较高。
结论
巨噬细胞和 γδ-T 细胞的增殖促进了 ZOL 诱导的颌骨坏死中的炎症反应。
方法
收集 2016 年 1 月至 2018 年 3 月颌骨坏死患者 20 例设为观察组，同期健康体检者 20 例设为对照组，另选 SD 大鼠 40 只设为观察组，非治疗 SD 大鼠 10 只设为对照组。分析颌骨坏死组织中 CD11b+Gr1hi 细胞和 γδ-T 细胞的分布和比例，检测 TNF-α、IL-1β、IFN-γ、CCL3、CCL4、IL-12、IL-13 水平，分析动物模型颌骨坏死组织中 CTSK、FGFR3、NF-κB、ERBB2IP 的表达。
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