mt2 通过清除 ros 抑制破骨细胞生成。

IF 0.7 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Acta Endocrinologica-Bucharest Pub Date : 2023-10-01 Epub Date: 2024-06-24 DOI:10.4183/aeb.2023.447
S Wei, K Liu, H Wu, J Hu, J He, G Li, B Liu, W Yang
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引用次数: 0

摘要

背景和目的:氧化应激下产生的活性氧(ROS)对破骨细胞的生成非常重要。作为金属硫蛋白(MT)家族的主要成员,金属硫蛋白2(MT2)可以清除成骨细胞中的ROS。然而,MT2在破骨细胞生成和破骨细胞前体(OCPs)中产生ROS的作用尚不清楚:在本研究中,我们首先调查了骨质疏松模型小鼠中 MT2 的表达水平。接下来,我们探讨了 MT2 在破骨细胞分化和 OCPs 产生 ROS 中的作用。最后,通过基于过氧化氢(H2O2)的拯救实验,进一步阐明了 ROS 在 MT2 调控的破骨细胞分化中的重要作用:结果:与假手术(Sham)小鼠相比,卵巢切除(OVX)小鼠的骨髓原发性破骨细胞(Ly6C+CD11b-)具有较高的 ROS 水平和较低的 MT2 表达。MT2过表达抑制成熟破骨细胞的形成,而MT2敲除则相反。此外,MT2 过表达抑制了 OCP 中 ROS 的产生,而 MT2 敲除则表现出相反的效果。值得注意的是,MT2过表达对破骨细胞生成和ROS产生的抑制作用在加入H2O2后被阻断:结论:MT2通过抑制OCPs中ROS的产生来抑制破骨细胞的生成,这表明在OCPs中上调MT2的策略可应用于破骨细胞性骨丢失的临床治疗。
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MT2 INHIBITS OSTEOCLASTOGENESIS BY SCAVENGING ROS.

Context and objective: Reactive oxygen species (ROS) produced under oxidative stress is important for osteoclastogenesis. As a major member of the metallothionein (MT) family, metallothionein2 (MT2) can scavenge ROS in osteoblasts. However, the role of MT2 in osteoclastogenesis and ROS production in osteoclast precursors (OCPs) is unknown.

Material and methods: In this study, we first investigated MT2 expression level in osteoporotic model mice. Next, we explored the roles of MT2 in osteoclastic differentiation and ROS production in OCPs. Ultimately, via rescue assays based on hydrogen peroxide (H2O2), the significance of ROS in MT-2-regulated osteoclastic differentiation was further elucidated.

Results: Compared with sham operated (Sham) mice, ovariectomized (OVX) mice displayed bone marrow primary OCPs (Ly6C+CD11b-) having higher ROS levels and lower MT2 expression. MT2 overexpression inhibited the formation of mature osteoclasts, while MT2 knockdown was contrary. Moreover, MT2 overexpression inhibited ROS production in OCPs, while MT2 knockdown exhibited the opposite effects. Notably, the inhibitory effect of MT2 overexpression on osteoclastogenesis and ROS production was blocked by the addition of H2O2.

Conclusion: MT2 inhibits osteoclastogenesis through repressing ROS production in OCPs, which indicates that the strategy of upregulating MT2 in OCPs may be applied to the clinical treatment of osteoclastic bone loss.

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来源期刊
Acta Endocrinologica-Bucharest
Acta Endocrinologica-Bucharest 医学-内分泌学与代谢
CiteScore
1.30
自引率
20.00%
发文量
53
审稿时长
6-12 weeks
期刊介绍: Acta Endocrinologica (Buc) is an international journal covering the fields of basic and clinical Endocrinology, Neuroendocrinology, Reproductive Medicine, Chronobiology, Human Ethology published quarterly Acta Endocrinologica (Buc) is the official international journal of the Romanian Society for Endocrinology. It continues the former Romanian Journal of Endocrinology
期刊最新文献
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