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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1439289

Identification of Biomarkers and Potential Drug Targets in Osteoarthritis Based on Bioinformatics Analysis and Mendelian Randomization

Provisionally accepted
Feng Cheng Feng Cheng 1,2Mengying Li Mengying Li 3Haotian Hua Haotian Hua 1Ruikun Zhang Ruikun Zhang 4Yiwen Zhu Yiwen Zhu 1Yingjia Zhu Yingjia Zhu 5Yang Zhang Yang Zhang 6Peijian Tong Peijian Tong 6*
  • 1 The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
  • 2 The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
  • 3 Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
  • 4 The Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
  • 5 Department of Gynecology, Hangzhou Women’s Hospital, Hangzhou, Jiangsu Province, China
  • 6 First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China

The final, formatted version of the article will be published soon.

    Background: Osteoarthritis (OA) can lead to chronic joint pain, and currently there are no methods available for complete cure. Utilizing the Gene Expression Omnibus (GEO) database for bioinformatics analysis combined with Mendelian randomization (MR) has been widely employed for drug repurposing and discovery of novel therapeutic targets. Therefore, our research focus is to identify new diagnostic markers and improved drug target sites.Methods: Gene expression data from different tissues of synovial membrane, cartilage and subchondral bone were collected through GEO data to screen out differential genes. Two-sample MR Analysis was used to estimate the causal effect of expression quantitative trait loci (eQTL) on OA. Through the intersection of the two, core genes were obtained, which were further screened by bioinformatics analysis for in vitro and in vivo molecular experimental verification. Finally, drug prediction and molecular docking further verified the medicinal value of drug targets.In the joint analysis utilizing the GEO database and MR approach, five genes exhibited significance across both analytical methods. These genes were subjected to bioinformatics analysis, revealing their close association with immunological functions. Further refinement identified two core genes (ARL4C and GAPDH), whose expression levels were found to decrease in OA pathology and exhibited a protective effect in the MR analysis, thus demonstrating consistent trends. Support from in vitro and in vivo molecular experiments was also obtained, while molecular docking revealed favorable interactions between the drugs and proteins, in line with existing structural data.Conclusions: This study identified potential diagnostic biomarkers and drug targets for OA through the utilization of the GEO database and MR analysis. The findings suggest that the ARL4C and GAPDH genes may serve as therapeutic targets, offering promise for personalized treatment of OA.

    Keywords: Gene Expression Omnibus, Bioinformatics analysis, Mendelian randomization, Osteoarthritis, biomarker, Brug target. 1.Introduction

    Received: 04 Jun 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Cheng, Li, Hua, Zhang, Zhu, Zhu, Zhang and Tong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Peijian Tong, First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.