抑制FABP4抑制去卵巢小鼠骨吸收,防止绝经后骨质疏松

IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Qian Xie, Xiangfu Du, Jianhui Liang, Yanni Shen, Yufan Ling, Zhengji Huang, Zekai Ke, Tai Li, Bing Song, Tailin Wu, Yan Wang, Huiren Tao
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引用次数: 0

摘要

绝经后骨质疏松症(PMOP)是一种由雌激素缺乏引起的女性疾病,其特征是骨量减少和骨折风险增加。脂肪酸结合蛋白4 (FABP4)是一种参与代谢和炎症的脂质结合蛋白,已成为代谢紊乱和骨吸收的关键调节因子;然而,其在ppu中的直接作用尚不清楚。在这里,我们发现PMOP患者的血清FABP4水平与骨密度呈负相关,在卵巢切除的小鼠中也观察到这种趋势。FABP4促进破骨细胞形成和骨吸收,但不影响成骨细胞分化。FABP4抑制剂BMS309403通过调节钙信号和抑制Ca2+-Calcineurin-NFATc1途径抑制破骨细胞分化。口服BMS309403可增加去卵巢小鼠的骨密度,但效果不如阿仑膦酸钠。值得注意的是,骨靶向给药BMS309403的疗效与阿仑膦酸钠相当。在这项工作中,我们证明FABP4是PMOP的关键介质,抑制它提供了一种有希望的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

FABP4 inhibition suppresses bone resorption and protects against postmenopausal osteoporosis in ovariectomized mice

FABP4 inhibition suppresses bone resorption and protects against postmenopausal osteoporosis in ovariectomized mice

Postmenopausal osteoporosis (PMOP) is a condition in women caused by estrogen deficiency, characterized by reduced bone mass and increased fracture risk. Fatty acid-binding protein 4 (FABP4), a lipid-binding protein involved in metabolism and inflammation, has emerged as a key regulator in metabolic disorders and bone resorption; however, its direct role in PMOP remains unclear. Here, we show that serum FABP4 levels in PMOP patients negatively correlate with bone mineral density, a trend also observed in ovariectomized mice. FABP4 promotes osteoclast formation and bone resorption without affecting osteoblast differentiation. The FABP4 inhibitor BMS309403 suppresses osteoclast differentiation by modulating calcium signaling and inhibiting the Ca2+-Calcineurin-NFATc1 pathway. Oral BMS309403 increases bone mineral density in ovariectomized mice, though less effectively than alendronate. Notably, bone-targeted delivery of BMS309403 achieves comparable efficacy to alendronate. In this work, we demonstrate that FABP4 is a critical mediator in PMOP and that its inhibition offers a promising therapeutic strategy.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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