In vivo identification of Bmp2-correlation networks during fracture healing by means of a limb-specific conditional inactivation of Bmp2

Specifically, activation and subsequent differentiation of periosteal progenitor cells requires Bmp2 signaling for activation of the osteo-chondrogenic pathway. Here, we explored the interactive transcriptional gene-gene interplays between Bmp2 and 150 known candidate genes during fracture repair. We constructed the interactive Bmp2 signaling pathways in vivo, by comparing gene expression levels prior and 24 h post femur fracture, in presence (wild type) and in absence of Bmp2 (Bmp2c/c;Prx1::cre limb-specific conditional knockout). Twenty-six differentially expressed genes (pre- vs. post-fracture), which demonstrated high correlations within each experimental condition, were used to construct the co-expression networks. Topological dynamic shifts across different co-expression networks characterized the 26 differentially expressed genes as non-redundant focal linking hubs, redundant connecting hubs, periphery genes, or non-existent. Top-ranked up- or down-regulated genes were identified and discussed. Protein-protein interactions in public databases support our findings. Thus, the co-expression networks from this study can be used for future experimental hypotheses.