Figure 3.

Bone Morphogenic Protein 2 (BMP-2) activation of signaling pathways. Once BMP-2 binds to the BMPRs located in lipid rafts, caveolae, and clathrin coated pits (CCPs), constitutively active BMPRII phosphorylates BMPRIa. This leads to downstream activation of the Smad pathway or the non-Smad pathways. In non-Smad signaling, the extracellular signal-related kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and the transforming growth factor-β-activated kinase 1/binding protein 1 (TAB1/TAK1) pathways are activated. All of these pathways, except for NF-kB, lead to an increased differentiation of MSCs and osteoprogenitors into osteoblasts.