Figure 3: Potential cross-talk between insulin/IGF-1, BMP2, and Wnt signaling pathways. BMP2 receptor signaling and the MEK/ERK branch of the insulin/IGF-1 signaling pathway converge on ERK1/2 kinase, which can modulate the activity of the master osteoblastogenic transcription factor, Runx2. Wnt and the PI3-K/Akt branch of the insulin/IGF-1 signaling pathway converge on GSK-3b, inhibiting GSK-3b kinase activity and reducing its constitutive phosphorylation of ß-catenin. Unphosphorylated ß-catenin is not readily degraded and can accumulate in the nucleus, where it acts as a proosteoblastogenic transcription factor by regulating transcription of Runx2 and other genes.