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西班牙女性严重骨关节炎与健康及骨质疏松受试者的代谢组学分析

Metabolomic Analysis of Severe Osteoarthritis in a Spanish Population of Women Compared to Healthy and Osteoporotic Subjects.

作者信息

Pertusa Clara, Mifsut Damián, Morales José Manuel, Tarín Juan J, Cano Antonio, Monleón Daniel, García-Pérez Miguel Ángel

机构信息

Research Unit, INCLIVA Health Research Institute, 46010 Valencia, Spain.

Orthopedic Surgery and Traumatology, Clinic Hospital, INCLIVA Institute of Health Research, 46010 Valencia, Spain.

出版信息

Metabolites. 2022 Jul 24;12(8):677. doi: 10.3390/metabo12080677.

DOI:10.3390/metabo12080677
PMID:35893245
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9329991/
Abstract

Bone pathologies such as osteoporosis (OTP) and osteoarthritis (OA) are rising in incidence with the worldwide rise in life expectancy. The diagnosis is usually obtained using imaging techniques such as densitometry, but with both being multifactorial diseases, several molecular mechanisms remain to be understood. Metabolomics offers the potential to detect global changes which can lead to the identification of biomarkers and a better insight in the progress of the diseases. Our aim was to compare the metabolic profiles of a cohort of 100 postmenopausal women, including subcapital hip fragility fracture patients, women with severe OA of the hip that required the implantation of a hip prosthesis and controls, to find altered metabolites and networks. Nuclear magnetic resonance (NMR) spectroscopy was used to obtain the metabolomic profiles of peripheral blood derived serum, and statistical analysis was performed using MATLAB V.6.5. 30 of the 73 metabolites analysed showed statistically significant differences in a 3-way ANOVA, and 11 of them were present in the comparison between OA and controls after adjustment by covariates, including amino acids, energy metabolism metabolites and phospholipid precursors. PLS-DA analysis shows a good discrimination between controls and fracture subjects with OA patients, and ROC curve analysis demonstrates that control and fracture subjects were accurately discriminated using the metabolome, but not OA. These results point to OA as an intermediate metabolic state between controls and fracture, and suggest that some metabolic shifts that happen after a fracture are also present at weaker intensity in the OA process.

摘要

随着全球预期寿命的增加,骨质疏松症(OTP)和骨关节炎(OA)等骨骼疾病的发病率正在上升。通常使用诸如骨密度测定等成像技术进行诊断,但由于这两种疾病都是多因素疾病,一些分子机制仍有待了解。代谢组学有潜力检测整体变化,从而有助于识别生物标志物并更好地洞察疾病进展。我们的目的是比较100名绝经后女性的代谢谱,包括股骨颈脆性骨折患者、需要植入髋关节假体的重度髋骨关节炎女性以及对照组,以找出改变的代谢物和代谢网络。使用核磁共振(NMR)光谱法获取外周血衍生血清的代谢组学谱,并使用MATLAB V.6.5进行统计分析。在73种分析的代谢物中,有30种在三因素方差分析中显示出统计学上的显著差异,其中11种在通过协变量调整后,在OA与对照组的比较中存在差异,包括氨基酸、能量代谢代谢物和磷脂前体。PLS-DA分析显示对照组与骨折受试者以及OA患者之间有良好的区分度,ROC曲线分析表明使用代谢组可以准确区分对照组和骨折受试者,但不能区分OA患者。这些结果表明OA是对照组和骨折之间的一种中间代谢状态,并表明骨折后发生的一些代谢变化在OA过程中也以较弱的强度存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97a0/9329991/e9c099a86f8a/metabolites-12-00677-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97a0/9329991/aed13c8f17b6/metabolites-12-00677-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97a0/9329991/e9c099a86f8a/metabolites-12-00677-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97a0/9329991/aed13c8f17b6/metabolites-12-00677-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97a0/9329991/e9c099a86f8a/metabolites-12-00677-g002.jpg

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