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基于整合代谢组学-脂质组学的绝经后骨质疏松症小鼠模型发病机制研究策略。

Integrative Bone Metabolomics-Lipidomics Strategy for Pathological Mechanism of Postmenopausal Osteoporosis Mouse Model.

机构信息

Institute of translational medicine, Shanghai University, Shanghai, 200444, China.

Graduate Management Unit, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.

出版信息

Sci Rep. 2018 Nov 7;8(1):16456. doi: 10.1038/s41598-018-34574-6.

Abstract

Osteoporosis, characterized by bone mass reduction and increased fractures, has become a global health problem that seriously affects the health of people, especially postmenopausal women; however, the current pathogenesis of postmenopausal osteoporosis (PMOP) has not been thoroughly elucidated to date. In this study, bilateral ovariectomy was performed to establish an OVX mouse model of osteoporosis. UPLC-Q-TOF-MS-based lipidomics in combination with metabolomics were used to analyze the femur tissue of osteoporosis mice. We found that 11 polar metabolites and 93 lipid metabolites were significantly changed and were involved in amino acid metabolism, nucleotide metabolism and lipid metabolism. Among the lipids, fatty acyls, glycerolipids, glycerophospholipids, sphingolipids and sterols showed robust changes. These results revealed that several metabolic disorders caused by changes in the hormone levels in OVX, especially disordered lipid metabolism, are closely related to the imbalance between bone resorption and formation and may underlie the development of PMOP. The data generated via lipidomics and metabolomics presented in this study shows good applicability and wide coverage in the construction of the metabolic profile of bone tissue. Therefore, this approach may provide the pathway focusing and data support at the metabolite level for the in-depth mechanism of PMOP.

摘要

骨质疏松症的特征是骨量减少和骨折风险增加,已成为全球范围内严重影响人们健康的问题,尤其是绝经后妇女;然而,目前绝经后骨质疏松症(PMOP)的发病机制尚未得到彻底阐明。在本研究中,通过双侧卵巢切除术建立了骨质疏松症小鼠模型。采用基于 UPLC-Q-TOF-MS 的脂质组学和代谢组学联合分析骨质疏松症小鼠的股骨组织。我们发现,11 种极性代谢物和 93 种脂质代谢物发生显著变化,这些代谢物参与了氨基酸代谢、核苷酸代谢和脂质代谢。在脂质中,脂肪酸酰基、甘油酯、甘油磷脂、鞘脂和甾醇表现出明显的变化。这些结果表明,OVX 引起的激素水平变化导致的几种代谢紊乱,特别是脂质代谢紊乱,与骨吸收和形成之间的失衡密切相关,可能是 PMOP 发生的基础。本研究中呈现的脂质组学和代谢组学数据在构建骨组织代谢图谱方面具有良好的适用性和广泛的覆盖范围。因此,这种方法可能为 PMOP 的深入机制提供了在代谢物水平上的关注点和数据支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c08/6220250/334bee74cc17/41598_2018_34574_Fig1_HTML.jpg

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