MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts
MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts
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MnTBAP 通过减少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
DOI：
10.1007/s00774-019-01038-4
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Lin, Dasheng
中科院分区：
文献类型：
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作者：
Cao, Xiangchang;Luo, Deqing;Lin, Dasheng
绝经后骨质疏松症的发生被认为与氧化应激密切相关。 Mn(III)四（4-苯甲酸）卟啉（MnTBAP）是一种新型超氧化物歧化酶（SOD）模拟物，可以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，目前尚不清楚MnTBAP是否对绝经后骨质疏松症的发生有影响。在这里，我们证明了 MnTBAP 可以抑制骨质流失和骨微结构改变，增加成骨细胞数量，同时减少破骨细胞数量，并提高去势大鼠模型中 BMP-2 的表达水平。此外，MnTBAP 还可以防止卵巢切除术和过氧化氢 (H2O2) 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，以剂量依赖性方式降低氧化应激对成骨细胞分化的影响并增加BMP-2表达水平。总而言之，我们的研究结果提供了新的见解，即 MnTBAP 通过减少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，并且可能是绝经后骨质疏松症治疗的潜在药物。
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.