Dataset Information

Proteomic and Acetylome Alterations in Obesity-related Osteoarthritic Mouse Cartilage

ABSTRACT: Male mice aged 4 weeks were housed under controlled conditions and assigned to either a normal diet or a high-fat diet for 16 weeks to establish an obesity model. At 12 weeks, osteoarthritis was induced using the destabilization of the medial meniscus procedure under anesthesia, while sham-operated mice served as controls. Eight weeks post-surgery, tibial cartilage tissues were collected, ensuring surrounding tissues were removed under a microscope. Tissues from 3-5 mice per group were pooled, and flash-frozen for subsequent lipidomic, proteomic, and acetylome analyses.

ORGANISM(S): Mus Musculus

SUBMITTER: Shunwu Fan

PROVIDER: PXD062707 | iProX | Tue Apr 08 00:00:00 BST 2025

REPOSITORIES: iProX

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Publications

Chondrocyte fatty acid oxidation drives osteoarthritis via SOX9 degradation and epigenetic regulation.

Mei Zixuan Z Yilamu Kamuran K Ni Weiyu W Shen Panyang P Pan Nan N Chen Huasen H Su Yingfeng Y Guo Lei L Sun Qunan Q Li Zhaomei Z Huang Dongdong D Fang Xiangqian X Fan Shunwu S Zhang Haitao H Shen Shuying S

Nature communications 20250527 1

Osteoarthritis is the most prevalent age-related degenerative joint disease and is closely linked to obesity. However, the underlying mechanisms remain unclear. Here we show that altered lipid metabolism in chondrocytes, particularly enhanced fatty acid oxidation (FAO), contributes to osteoarthritis progression. Excessive FAO causes acetyl-CoA accumulation, thereby altering protein-acetylation profiles, where the core FAO enzyme HADHA is hyperacetylated and activated, reciprocally boosting FAO a ...[more]

PMID: 40425566

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Project description:Objective: To Identify gene changes in the medial tibial plateau of articular cartilage at 2, 4 and 8 weeks after destabilisation of the medial meniscus (DMM) in mice and compare our data set with previously published sets to ascertain dysregulated pathways and genes in osteoarthritis. Materials and methods: RNA was extracted from the ipsilateral and contralateral medial tibial plateaus, amplified, labelled and hybridized on Illumina WG_v2 microarrays. Results were confirmed by RT-PCR for selected genes. Results: Transcriptional analysis and network reconstruction revealed changes in extracellular matrix (ECM) and cytoskeletal genes induced by DMM. TGFalpha signalling pathway and complement and coagulation cascade genes were regulated at 2 weeks. Fibronectin (FN1) is a hub in a reconstructed network of potential protein-protein interactions at 2 weeks. Regulated genes decrease over time and by eight weeks fibromodulin (FMOD) and tenascin N (TNN) are the only dysregulated genes present in the DMM operated knees. Comparison with human and rodent published gene sets discovered genes overlapping between our array and 6 others. Conclusions: Cartilage contributes a minute percentage to the RNA extracted from the whole joint (>0.2%), yet is sensitive to changes in gene expression post-DMM. The post-DMM transcriptional reprogramming wanes over time and dissipates by 8 weeks. Common pathways between published gene sets include focal adhesion, regulation of actin cytoskeleton and TGFalpha. Common genes include Jagged 1 (Jag1), Tetraspanin 2 (Tspan2), neuroblastoma, suppression of tumourigenicity 1 (Nbl1) and N-myc downstream regulated gene 2 (Ndrg2). The concomitant genes and pathways we identify are novel and warrant further investigation as biomarkers or modulators of osteoarthritis. In total 18 samples. Each sample was a pool of the medial tibial plateau of 8 mice. Two categories (Treated and untreated) with three biological replicates each and three time points (2, 4 and 8 weeks post-surgery).

Dataset Information

Proteomic and Acetylome Alterations in Obesity-related Osteoarthritic Mouse Cartilage

Publications

Chondrocyte fatty acid oxidation drives osteoarthritis via SOX9 degradation and epigenetic regulation.

Similar Datasets

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