Work

Mechanisms and Functions of the Macrophage Metabolism-immune Regulation Axis in Osteoarthritis—based on the JUN/ATG7 Subtyping Model From Single-cell Sequencing

Year: 2026

Type: article

Abstract: Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by dysregulation of the joint immune microenvironment, in which macrophages play a pivotal role. This study aimed to elucidate the mechanisms by which macrophage mitochondrial function regulates immune phenotypes to drive OA progression. Through integrated analysis of single-cell RNA sequencing and bulk transcriptome data from the GEO database, we identified JUN and ATG7 as key macrophage genes associated with mitochondrial autophagy and immune regulation. A diagnostic model based on LASSO regression (RiskScore = JUN × (-0.165) + ATG7 × 0.151) demonstrated high accuracy (AUC = 0.99 in training and 0.93 in validation sets). Mechanistically, JUN and ATG7 form an “inflammation-metabolism” regulatory axis: JUN promotes pro-inflammatory M1 polarization and enriches pathways like TNF and IL-17, while ATG7 supports anti-inflammatory M2 polarization and metabolic pathways such as PI3K-Akt. Cellular and animal experiments confirmed that modulating JUN/ATG7 expression influences macrophage polarization and ameliorates cartilage degeneration. This study reveals a mitochondria-immune regulatory axis centered on JUN/ATG7 in OA macrophages, offering new insights for molecular subtyping, early diagnosis, and targeted therapeutic strategies.

Source: Inflammation

DOI: 10.1007/s10753-026-02572-w