Figure 2
From: The biological function of type I receptors of bone morphogenetic protein in bone
A proposed mechanism diagram describing the crosstalk between osteoblastic BMP signaling (mainly via ALK3) and canonical Wnt signaling in regulating bone homeostasis. After being activated by BMPs, the BMPRs in the cell surface induce intracellular BMP signaling, including both Smad-dependent signaling and non-Smad-dependent signaling. Then, these activated signaling pathways initiate the expression of canonical Wnt inhibitors (DKK1 and SOST), which influence the binding of Wnt ligands to their receptor complexes consisting of low-density lipoprotein (LDL) receptor-related protein 5/6 (LRP5/6) and frizzled (Fzd) receptors. As a result, cytoplasmic β-catenin will be degraded, and its transcriptional regulation will be diminished, resulting in a downregulation of Wnt/β-catenin signaling activity. The balance between BMP and canonical Wnt signaling affects bone development and homeostasis by regulating both osteogenesis and osteoclastogenesis.
