Fig. 3

Downregulated expression of the MKK3/p38 MAPK/PCNA pathway in humeri from Enpp1 KO mice A Volcano plot shows proteins in the humeri of Enpp1 KO mice, which cross the significance threshold with displaying decreased 1268 proteins and increased 111 proteins in humeri of KO mice compared with that in WT mice. Enpp1 protein expression was significantly lower in KO than in the WT group. B Heatmap of 1379 differential expression proteins in the humeri of WT and Enpp1 KO mice (p < 0.005). Decreased expression in blue and increased expression in red. C Gene Ontology biological process analysis showed that differently expressed proteins are involved in the MAPK signaling and MAPK signaling pathway was significantly downregulated in Enpp1-deficient humeri when compared to that in the WT group (p = 10^−37.9533). D Kyoto Encyclopedia of Genes and Genomes pathway analysis unveiled that the expression of the MAPK signaling pathway was downregulated in the humeri of Enpp1 knockout mice compared to that in the humeri of mice in the WT group. E Protein–protein interaction network diagram of key modules was related to MAP3K5. F Immunoblot result of MKK3, phosphorylated p38 MAPK, and PCNA of the humeri from WT and Enpp1 KO mice (n = 3). To improve clarity and conciseness, blots are cropped to the location of the target protein band