Fig. 4.

Enpp1 deletion caused unbalanced ATP metabolism, downregulated AMPK signaling pathway and chondrocyte apoptosis in knee articular cartilage: A Volcano plot showed 149 downregulated differential proteins and 38 upregulated differential proteins (p < 0.05, n ≥ 4). B Heatmap of 187 differential expression proteins in WT and Enpp1^−/− cartilages (p < 0.05, n ≥ 4). C KEGG pathway analysis of differential expression proteins (p < 0.05, n ≥ 4). D Bar graph of enriched pathways (Pyrimidine metabolism, AMPK signaling pathway, Apoptosis-multiple species, PI3K-Akt signaling pathway and mTOR signaling pathway) selected from Fig. C (p < 0.05, n ≥ 4). E Network of enriched pathways (pyrimidine metabolism, AMPK signaling pathway, Apoptosis-multiple species, PI3K-Akt signaling pathway and mTOR signaling pathway) chosen from Fig. C (p < 0.05, n ≥ 4). F Bar graph of enriched pathways (pyrimidine metabolism and AMPK signaling pathway) (p < 0.05, n ≥ 4). G Protein–protein interaction network diagram of key modules was related to Casp7, Xiap, Itga4 and Itgb4. Enpp1, ectonucleotide pyrophosphatase/phosphodiesterase 1; ATP, Adenosine triphosphate; AMPK, AMP-activated protein kinase; WT, wild type; KEGG, Kyoto Encyclopedia of Genes and Genomes; PI3K, Phosphoinositide 3-Kinase; Akt, protein kinase B; mTOR, mammalian target of rapamycin; Casp7, caspase 7; Xiap, X-linked inhibitor-of-apoptosis protein; Itga4, integrin a4; Itgb4, integrin beta4