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

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.

UPLC–QTOF/MS‐based metabolomics reveals the mechanism of chronic unpredictable mild stress‐induced hypertension in rats

“…As is shown in Figure c, >80% of the RSD values (89.65% in the positive ion mode and 94.82% in the negative ion mode) of the QC samples were <20%. These results demonstrate that the stability of the proposed method was sufficient (Zhao et al, ). The entire normalized data from all samples were imported into SIMCA‐P program (version 11) to perform PCA and PLS‐DA.…”

High-Throughput Metabolomics Discovers Metabolic Biomarkers and Pathways to Evaluating the Efficacy and Exploring Potential Mechanisms of Osthole Against Osteoporosis Based on UPLC/Q-TOF-MS Coupled With Multivariate Data Analysis

“…Recently, modern high-throughput technology including nuclear magnetic resonance spectroscopy (NMR), gas chromatography mass spectrometry (GC-MS), liquid chromatography mass spectrometry (LC-MS), or capillary electro-phoresis mass spectrometry (CE-MS) coupled with multivariate analysis was successfully performed multiparametric metabolic responses to pathophysiological and environmental perturbations in metabolomics research ( Sun et al, 2013b ; Zhang et al, 2017 ; Sun et al, 2019 ; Zhao et al, 2020 ). It has been widely used in early diagnosis, disease staging, and treatment evaluation of osteoporosis ( Lv et al, 2016 ; Zhao et al, 2018 ; Xia et al, 2019 ; Zhang et al, 2019 ; Ye et al, 2020 ). Animal model of OP can be set up by traditional castration surgery and modern study ( Tella and Gallagher, 2014 ; Drake et al, 2015 ).…”

Perturbations of Lipids and Oxidized Phospholipids in Lipoproteins of Patients with Postmenopausal Osteoporosis Evaluated by Asymmetrical Flow Field-Flow Fractionation and Nanoflow UHPLC–ESI–MS/MS

“…While HexCer d18:1/16:1 was increased in HDL and decreased in LDL, three other HexCer species (d18:1/22:0, d18:1/24:0, and d18:1/24:1) showed the exact opposite pattern. HexCer belongs to a group of glycosphingolipids which is considered to be essential in the formation of osteoblasts [38], and an increased level of glycosphingolipids can accelerate osteoblast differentiation, which may disturb the balance between bone resorption and formation in bone tissue [10]. Although the four HexCer species in this study showed different trends in both lipoproteins, the change in the total amount of HexCer in each lipoprotein fraction was negligible ( Figure S3) due to compositional alterations.…”

“…A recent report on the aging-related lipidomic changes in human bone mesenchymal stem cells (BMSCs) showed that PC, PE, and Cer levels were significantly elevated with aging [33]. Cer levels were reported to be increased in the femur of a PMOp mouse model [10] and in the serum (Cer d18:0/18:0) of an ovariectomy-induced osteoporosis rat model [34]. These results are in line with the observed increase in most Cer species in patients with PMOp.…”

“…Since the oxidation of lipoproteins occurs at lipids, bone loss should be associated with alterations in circulating lipid profiles, especially oxidized lipids. Indeed, a correlation between lipid changes and postmenopausal osteoporosis (PMOp) has been found in the femur tissue of osteoporotic mice [10] and human plasma samples [11,12]. Recently, it has been found that inflammatory bioactive lipids, which promote atherosclerosis, also induce bone loss [13], and that oxidized LDL is pathogenically associated with the loss of bone mass [14].…”