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

MnTBAP 通过降低成骨细胞中的线粒体氧化应激来抑制卵巢切除大鼠的骨质流失

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作者:Xiangchang Cao, Deqing Luo, Teng Li, Zunxian Huang, Weitao Zou, Lei Wang, Kejian Lian, Dasheng Lin

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 (H2O2). 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.

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