Figure 7.
Schematic model of the involvement of LRP6 in the PTH-stimulated anabolic bone effect. PTH-stimulated complex formation of PTH–PTH1R–LRP6 results in the activation of cAMP-PKA and β-catenin-Tcf/Lef signaling pathways in osteoblastic lineage cells. In earlier stages of osteoblastic lineage cells, LRP6-mediated activation of both pathways by PTH promotes the survival and differentiation of osteoblasts, leading to increased osteoblastic bone formation (A). In osteocytes, LRP6-mediated activation of cAMP signaling pathway by PTH inhibits MEF2 transcription factor–stimulated activity of Sost transcription and reduces sclerostin production, leading to increased osteoblastic bone formation (B).