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

Abstract

Bmp2 is known to play an essential role in the initiation of fracture healing via periosteal activation. 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.