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.
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.