Role of menin in bone development.

Menin function is related to transcriptional regulation and cell cycle control and it physically and functionally interacts with osteotropic transcription factors, such as Smad1/5, Smad3, Runx2 and JunD. Menin promotes the commitment of pluripotent mesenchymal stem cells to the osteoblast lineage, mediated by interactions between menin and the BMP signaling molecules, Smad1/5, or Runx2. On the other hand, in mature osteoblasts the interaction of menin and the TGF-beta/Smad3 pathway counteracts the BMP-2/Smad1/5- and Runx2-induced transcriptional activities leading to inhibition of late stage osteoblast differentiation. Moreover, menin suppresses osteoblast maturation partly by inhibiting the differentiation actions of JunD. In conclusion, menin plays an important role in osteoblastogenesis and osteoblast differentiation.