Osteogenic Transcription Factor Runx2 Regulates Components of the Fibroblast Growth Factor/Proteoglycan Signaling Axis in Osteoblasts

The model depicts several well-known aspects of the FGF signaling cascade including the synergy between FGF signaling and proteoglycans, as well as downstream effects on FGF signaling on MAPK and CDK related pathways. We propose that Runx2 may participate in two distinct feed-back loops. In actively dividing cells, FGF2 is mitogenic and activates MAPKs and CDKs. This activation may both promote and attenuate Runx2 activity to generate short-term changes in proteoglycan expression that transiently modulate responsiveness to FGF2. In post-proliferative cells, FGF2 functions anabolically and CDK effects on Runx2 are blocked by CDK inhibitors (CKIs). Consequently, the FGF/MAPK/Runx2 pathway may generate a long-term sustained response in which Runx2 modulates a program of proteoglycan expression to promote osteoblast maturation. The ideas presented in the model are consistent with references presented in the main text, but remain to be experimentally tested.

Publication

The Osteogenic Transcription Factor Runx2 Regulates Components of the Fibroblast Growth Factor/Proteoglycan Signaling Axis in Osteoblasts. () Nadiya M. Teplyuk, et al. J Cell Biochem. ;107(1):144-154. Figure: F8. Homo sapiens

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