IRS2/FOXO1 mitigates osteoarthritis by regulating chondrocyte autophagy and mitochondrial function.

ABSTRACT:

Purpose

Osteoarthritis (OA) is a debilitating joint disease with no effective cure. This study investigates the role of Insulin Receptor Substrate 2 (IRS2) in OA and its potential as a therapeutic target.

Methods

Transcriptomic analysis of OA-related datasets (GSE178557, GSE169077, GSE64394, GSE57218) was conducted to identify differentially expressed genes (DEGs), with KEGG pathway analysis highlighting the PI3K/AKT pathway. In vivo, the destabilization of the medial meniscus (DMM) OA mouse model was used to assess IRS2 expression through histology, qPCR, and Western blot. IRS2 was overexpressed in primary mouse chondrocytes via adenoviral transfection, with proliferation, apoptosis, and autophagy assessed by EdU, Annexin V/PI staining, and autophagy-related protein analysi

SUBMITTER: Qin C 

PROVIDER: S-EPMC12465773 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature