New insights of periosteum proteomics analysis on pathogenesis of congenital pseudarthrosis of tibia in children.

RATIONALE: The exact etiology and pathogenesis of CPT are not clear. Quantitative proteomics analysis plays a vital role in disease pathology research. TMT-based proteomics technique were employed to identify and analyze the differentially expressed proteins in the tibia periosteum tissues of CPT.

METHODS: The samples were divided into three groups: CPT with NF1 group, CPT without NF1 group (non-NF1-CPT), and control group (patients with open tibial fracture). A fold change ≥ 1.5 or ≤ 0.66, and P-value <0.05 were used as the thresholds to screen differentially expressed proteins (DEPs). Subsequently, bioinformatics resources such as online tools DAVID and String were subjected to generate GO annotation, KEGG pathways enrichment and PPI network for these DEPs.

RESULTS: According to statistics, a total of 347 proteins differentially expressed in NF1-CPT groups, 212 of which were up-regulated and 135 were down-regulated. There were more DEPs in nonNF1-CPT groups, we identified 467 DEPs, including 281 up-regulated and 186 down-regulated. Among of them, NF1-CPT groups and nonNF1-CPT groups shared 231 DEPs, the remaining 230 DEPs showed the same expression trend in the two disease groups, 117 were up-regulated and 113 were down-regulated. In particular, 116 proteins were altered only in NF1-CPT groups (94 were up-regulated and 22 were down-regulated), while 236 proteins were altered only in nonNF1-CPT groups (164 were up-regulated and 72 were down-regulated). Finally, compared with nonNF1-CPT, 47 proteins changed 1.5-fold and p-Value<0.05 in NF1-CPT groups.

CONCLUSIONS: To sum up, we found that common differential proteins in periosteum of NF1-CPT and nonNF1-CPT are mainly involved in cell matrix assembly, cell adhesion, AKT-PI3K signal pathway activation and vascular agglutination, which indicate that these are the pathological characteristics of CPT. The osteogenic ability is weak, the osteoclastic ability is strong, the vascular lumen is narrow, the invasive growth and the proliferation of fibroblasts are enhanced in CPT patients.