ORIGINAL RESEARCH article
Front. Med.
Sec. Geriatric Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1552029
This article is part of the Research TopicFrom Crosstalk Among Cell Populations in the Microenvironment of Bone Degenerative Diseases to the Novel Therapeutic ApproachesView all 6 articles
Integrative Analysis of Bulk and Single-cell RNA Sequencing Data Reveals Increased Arachidonic Acid Metabolism in Osteoarthritic Chondrocytes
Provisionally accepted
- 1Southern Medical University, Guangzhou, China
- 2Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
- 3Department of Infectious Diseases, The First Affiliated Hospital of USTC, he fei, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abnormal lipid metabolism in chondrocytes, especially arachidonic acid (AA) metabolism, has attracted considerable attention in promoting osteoarthritis (OA) progression. However, the metabolic regulation of chondrocytes in OA remains to be investigated.Bulk RNA sequencing (RNA-seq) data and single-cell RNA sequencing (scRNA-seq) data of human knee cartilage were downloaded from public databases. Gene set variation analysis (GSVA) and weighted correlation network analysis (WGCNA) were used to explore functional regulation and gene expression characterization. A reference gene set from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to validate metabolic changes. CellChat analysis was performed to investigate the communication among osteoarthritic chondrocytes. Human immortalized chondrocytes were stimulated with macrophage migration inhibitory factor (MIF), then quantitative real-time PCR (qPCR) and western blot (WB) analysis were used to detect transcription or translation levels of genes.Enzyme linked immunosorbent assay (ELISA) was used to measure AA content. Cartilage from OA patients was collected for immunohistochemistry (IHC) to validate protein expression.Functional analysis revealed significant activation of the AA metabolic pathway was significantly enriched in the cluster of proliferative chondrocytes (ProCs). CellChat analysis indicated that the incoming signals of MIF increased in ProCs, and the expressions of extracellular signalregulated kinase (ERK) and phospholipase A2 group IVA (PLA2G4A) were upregulated.Moreover, functional analysis showed that the ERK pathway was enriched in ProCs. Cell experiments indicated MIF stimulation elevated phospho-ERK (p-ERK) and PLA2G4A expression and AA content. IHC showed p-ERK and PLA2G4A were significantly activated in OA cartilage. MIF also upregulated interleukin 1β (IL1B) and matrix metalloproteinase 13 (MMP13) expression.Our study shows that MIF stimulation of chondrocytes can activate the ERK/PLA2G4A signaling pathway and increase AA production. ProCs located in the proliferative layer of cartilage are likely the main cells executing this mechanism. Therefore, targeting and inhibiting MIF signaling in chondrocytes, especially in ProCs, could be a novel strategy for the prevention and treatment of OA.
Keywords: MIF, Arachidonic Acid, Osteoarthritis, chondrocyte, Bulk RNA sequencing, single-cell RNA sequencing
Received: 27 Dec 2024; Accepted: 21 Apr 2025.
Copyright: © 2025 JIANG, Wu, Zhong, Chen, Luo, Jiang and Tao. 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: YONG JIANG, Southern Medical University, Guangzhou, 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.