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ORIGINAL RESEARCH article

Front. Med.
Sec. Rheumatology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1448937

Enhanced Understanding of Cinnamaldehyde’s Therapeutic Potential in Osteoarthritis through Bioinformatics and Mechanistic Validation of Its Anti-Apoptotic Effect

Provisionally accepted
Chengai Wu Chengai Wu 1*Yueyang Sheng Yueyang Sheng 1Rui-Qing Zhai Rui-Qing Zhai 2Shan Li Shan Li 1Xinyu Wang Xinyu Wang 1Ying Wang Ying Wang 1Zheng-Guo Cui Zheng-Guo Cui 3Chao Wang Chao Wang 1Qianqian Wang Qianqian Wang 1Yanzhuo Zhang Yanzhuo Zhang 1
  • 1 Department of Molecular Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing, China
  • 2 Harbin Medical University, Harbin, Heilongjiang, China
  • 3 University of Fukui, Fukui, Fukui, Japan

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

    Osteoarthritis (OA) represents a globally prevalent joint disorder, affecting an estimated 240 million individuals worldwide. Cinnamaldehyde, recognized for its extensive anti-inflammatory and anti-aging pharmacological properties across various cell types, has yet to be evaluated for its potential effects on apoptosis in OA chondrocytes. This study aimed to assess the effectiveness of cinnamaldehyde in alleviating knee osteoarthritis by reducing chondrocyte apoptosis. Initially, bioinformatics analysis was employed to identify apoptosis-associated differentially expressed genes (APDEGs). These findings led to an examination of gene expression datasets GSE55235 and GSE114007 utilizing weighted gene co-expression network analysis (WGCNA). The gene modules highlighted were subsequently cross-referenced with APDEGs to pinpoint those specific to OA. LASSO regression analysis was then applied to construct a risk model, which, coupled with datasets GSE114007, GSE55457, and GSE12021, supported ROC validation. Cellular experiments and blood analyses from OA patients revealed that cinnamaldehyde administration could remediate the abnormal expression of pivotal apoptosis-related genes in these subjects. Our results suggested that cinnamaldehyde may influence knee osteoarthritis through its regulatory impact on specific apoptosis-related genes, namely ZFAND5, BCL6, ELL2, FOSL2, MARCKS, and SGCD. These insights provide substantial theoretical backing for the clinical application of cinnamaldehyde in OA treatment. Additionally, the identification of three novel apoptotic targets in OA chondrocytes-ZFAND5, ELL2, and SGCD-highlights potential therapeutic avenues for future OA interventions.

    Keywords: Osteoarthritis, Cinnamaldehyde, Apoptosis, Chondrocytes, bioinformatics, Gene Expression

    Received: 24 Jun 2024; Accepted: 04 Sep 2024.

    Copyright: © 2024 Wu, Sheng, Zhai, Li, Wang, Wang, Cui, Wang, Wang and Zhang. 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: Chengai Wu, Department of Molecular Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing, 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.