Assessing the causal relationship between plasma proteins and osteoporosis: novel insights into pathological mechanisms and therapeutic implications.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Osteoporosis International Pub Date : 2024-11-01 Epub Date: 2024-08-09 DOI:10.1007/s00198-024-07225-y
Liang Wang, Xiangyun Guo, Jinran Qin, Zikai Jin, Qingqing Liu, Chuanrui Sun, Kai Sun, Linghui Li, Xu Wei, Yili Zhang
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引用次数: 0

Abstract

Identifying dysregulated plasma proteins in osteoporosis (OP) progression offers insights into prevention and treatment. This study found 8 such proteins associated with OP, suggesting them as therapy targets. This discovery may cut drug development costs and improve personalized treatments.

Purpose: This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets.

Methods: To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein-protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets.

Results: In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets.

Conclusions: The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs.

Abstract Image

评估血浆蛋白与骨质疏松症之间的因果关系:对病理机制和治疗意义的新见解。
识别骨质疏松症(OP)进展过程中失调的血浆蛋白可为预防和治疗提供启示。本研究发现了 8 种与骨质疏松症相关的蛋白,并将其作为治疗靶点。目的:本研究旨在利用基于汇总数据的孟德尔随机化(SMR)和共定位分析方法,确定骨质疏松症的潜在治疗靶点。此外,我们还试图探索这些药物靶点的生物学意义和药理学价值:为了确定 OP 的潜在治疗靶点,我们进行了 SMR 和共定位分析。血浆蛋白(pQTL、暴露)数据来自 Ferkingstad 等人的研究(n = 35559)。骨矿物质密度(BMD,结果)的汇总统计数据来自 GWAS Catalog(n = 56,284)。此外,我们还利用富集分析、蛋白质-蛋白质相互作用(PPI)网络分析、药物预测和分子对接来进一步分析这些药物靶点的生物学意义和药理学价值:结果:在SMR分析中,虽然有20个蛋白质显示出重要意义,但只有8个潜在药物靶点(GCKR、ERBB3、CFHR1、GPN1、SDF2、VTN、BET1L和SERPING1)获得了共定位支持(PP.H4 > 0.8)。这些蛋白质在生物学意义上与免疫功能密切相关。分子对接也证明了药物与蛋白质的良好结合,这与现有的结构数据一致,进一步证实了这些靶点的药理学价值:研究发现了 8 个潜在的 OP 药物靶点。这些潜在靶点被认为在临床试验中有更大的成功几率,从而有助于确定 OP 药物开发的优先次序并降低开发成本。
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来源期刊
Osteoporosis International
Osteoporosis International 医学-内分泌学与代谢
CiteScore
8.10
自引率
10.00%
发文量
224
审稿时长
3 months
期刊介绍: An international multi-disciplinary journal which is a joint initiative between the International Osteoporosis Foundation and the National Osteoporosis Foundation of the USA, Osteoporosis International provides a forum for the communication and exchange of current ideas concerning the diagnosis, prevention, treatment and management of osteoporosis and other metabolic bone diseases. It publishes: original papers - reporting progress and results in all areas of osteoporosis and its related fields; review articles - reflecting the present state of knowledge in special areas of summarizing limited themes in which discussion has led to clearly defined conclusions; educational articles - giving information on the progress of a topic of particular interest; case reports - of uncommon or interesting presentations of the condition. While focusing on clinical research, the Journal will also accept submissions on more basic aspects of research, where they are considered by the editors to be relevant to the human disease spectrum.
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