PKM2 is a Novel Osteoporosis-Associated Protein in Chinese.

IF 1.5 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Endocrine Research Pub Date : 2024-02-01 Epub Date: 2024-01-30 DOI:10.1080/07435800.2024.2310818
Qing Xu, Chun-Hui Li, Chang-Hua Tang, Xiao-Li Huang, Long-Fei Wu, Xu Zhou, Shu-Feng Lei, Fei-Yan Deng
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Abstract

                       Purpose:Osteoporosis is characterized by low bone mineral density (BMD) and high risk of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. This study was to identify PBM-expressed proteins significant for osteoporosis in Chinese Han elderly population (>65 years), and focused on two phenotypes of osteoporosis: low BMD and OF.

Methods: Label-free quantitative proteomics was employed to profile PBM proteome and to identify differentially expressed proteins (DEPs) between OF (N=27) vs. non-fractured (NF, N=24) subjects and between low BMD (N=12) vs. high BMD (N=12) subjects in women. Western blotting (WB) was conducted to validate differential expression, and ELISA to evaluate translational value for secretory protein of interest.

Results: We discovered 59 DEPs with fold change (FC)>1.3 (P<1×10-5), and validated the significant up-regulation of pyruvate kinase isozyme 2 (PKM2) with osteoporosis (P<0.001). PKM2 protein upregulation with OF was replicated with PBM in men (P=0.04). Plasma PKM2 protein level was significantly elevated with OF in an independent sample (N=100, FC=1.68, P=0.01). Pursuant functional assays showed that extracellular PKM2 protein supplement not only promoted monocyte trans-endothelial migration, growth, and osteoclast differentiation (marker gene expression), but also inhibited osteoblast growth, differentiation (ALP gene expression), and activity.

Conclusion: The above findings suggest that PKM2 protein is a novel osteoporosis-associated functional protein in Chinese Han elderly population. It may serve as a risk biomarker and drug target for osteoporosis.

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PKM2 是一种新型的中国骨质疏松症相关蛋白
目的:骨质疏松症以骨矿物质密度(BMD)低和骨质疏松性骨折(OF)风险高为特征。外周血单核细胞(PBM)可分化为破骨细胞,从而吸收骨质。本研究旨在鉴定中国汉族老年人群(年龄大于 65 岁)中对骨质疏松症有重要影响的 PBM 表达蛋白,重点关注骨质疏松症的两种表型:低 BMD 和 OF:方法:采用无标记定量蛋白质组学分析 PBM 蛋白体组,并鉴定 OF(27 例)与非骨折(24 例)受试者之间以及女性低 BMD(12 例)与高 BMD(12 例)受试者之间的差异表达蛋白(DEPs)。我们进行了免疫印迹(Western blotting,WB)以验证差异表达,并用酶联免疫吸附试验(ELISA)评估相关分泌蛋白的转化价值:结果:我们发现了59个折叠变化(FC)大于1.3的DEPs(PC结论:上述结果表明,PKM2的表达与PKM3的表达存在差异:上述发现表明,PKM2 蛋白是中国汉族老年人群中一种新型的骨质疏松症相关功能蛋白。它可作为骨质疏松症的风险生物标志物和药物靶点。
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来源期刊
Endocrine Research
Endocrine Research 医学-内分泌学与代谢
CiteScore
4.30
自引率
0.00%
发文量
10
审稿时长
>12 weeks
期刊介绍: This journal publishes original articles relating to endocrinology in the broadest context. Subjects of interest include: receptors and mechanism of action of hormones, methodological advances in the detection and measurement of hormones; structure and chemical properties of hormones. Invitations to submit Brief Reviews are issued to specific authors by the Editors.
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