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MnTBAP 通过减少成骨细胞中线粒体氧化应激来抑制去卵巢大鼠的骨丢失。

MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts.

机构信息

Huangshi Central Hospital (Affiliated Hospital of Hubei Polytechnic University), Edong Healthcare Group, Huangshi, China.

Department of Orthopaedic Surgery, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, China.

出版信息

J Bone Miner Metab. 2020 Jan;38(1):27-37. doi: 10.1007/s00774-019-01038-4. Epub 2019 Sep 6.

Abstract

The development of postmenopausal osteoporosis is thought to be closely related to oxidative stress. Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase (SOD) mimetic, could protect osteoblasts from cytotoxicity and dysfunction caused by oxidative stress. However, it is still unclear whether MnTBAP has effect on the development of postmenopausal osteoporosis. Here, we demonstrated that MnTBAP can inhibit bone mass loss and bone microarchitecture alteration, and increase the number of osteoblasts while reducing osteoclasts number, as well as improve the BMP-2 expression level in ovariectomized rat model. Additionally, MnTBAP can also prevent oxidative stress status up-regulation induced by ovariotomy and hydrogen peroxide (HO). Furthermore, MnTBAP reduced the effect of oxidative stress on osteoblasts differentiation and increased BMP-2 expression levels with a dose-dependent manner, via reducing the levels of mitochondrial oxidative stress in osteoblasts. Taken together, our findings provide new insights that MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts, and maybe a potential drug in postmenopausal osteoporosis therapy.

摘要

绝经后骨质疏松症的发展被认为与氧化应激密切相关。Mn(III)四(4-苯甲酸)卟啉(MnTBAP)是一种新型的超氧化物歧化酶(SOD)模拟物,可保护成骨细胞免受氧化应激引起的细胞毒性和功能障碍。然而,MnTBAP 是否对绝经后骨质疏松症的发展有影响仍不清楚。在这里,我们证明 MnTBAP 可以抑制骨量丢失和骨微结构改变,增加成骨细胞数量,减少破骨细胞数量,并提高去卵巢大鼠模型中 BMP-2 的表达水平。此外,MnTBAP 还可以预防卵巢切除术和过氧化氢(HO)引起的氧化应激状态上调。此外,MnTBAP 通过降低成骨细胞中线粒体氧化应激水平,以剂量依赖的方式减少氧化应激对成骨细胞分化的影响,并增加 BMP-2 的表达水平。综上所述,我们的研究结果提供了新的见解,即 MnTBAP 通过降低成骨细胞中线粒体氧化应激来抑制去卵巢大鼠的骨丢失,并且可能是绝经后骨质疏松症治疗的一种潜在药物。

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