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

机译:整合骨代谢组学—绝经后骨质疏松症小鼠模型病理机制的脂蛋白学策略

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摘要

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.
机译:以骨量减少和骨折增加为特征的骨质疏松症已经成为严重影响人们尤其是绝经后妇女健康的全球性健康问题。然而,迄今为止,绝经后骨质疏松症(PMOP)的当前发病机理尚未得到充分阐明。在这项研究中,进行了双侧卵巢切除术以建立骨质疏松症的OVX小鼠模型。基于UPLC-Q-TOF-MS的脂质组学与代谢组学相结合,用于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种脂质代谢物发生了显着变化,并参与了氨基酸代谢,核苷酸代谢和脂质代谢。在脂质中,脂肪酰基,甘油脂,甘油磷脂,鞘脂和固醇表现出强烈的变化。这些结果表明,由OVX激素水平变化引起的几种代谢紊乱,尤其是脂质代谢紊乱,与骨吸收和形成之间的不平衡密切相关,可能是PMOP发生的基础。本研究中通过脂质组学和代谢组学产生的数据显示出良好的适用性,并且在骨组织代谢谱的构建中具有广泛的覆盖范围。因此,该方法可为代谢物的深入机制提供代谢产物水平上的途径聚焦和数据支持。

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