New Avenues in the LRP5-mediated Bone Mass Acquisition

Je-Yong Choi
2012 Korean Journal of Bone Metabolism  
Lipoprotein receptor-related protein (LRP5) signaling is well correlated with the bone mass in both human and mice. Loss-of-function mutations of LRP5 result in osteopenia or osteoporosis. In contrast, gain-of-function mutations show high bone mass phenotype. To elucidate the molecular mechanism of the LRP5-mediated bone mass acquisition, several groups have genetically dissected the Wingless and Int-1 (Wnt) -catenin signaling pathway using osteoblast-lineage specific Cre mice. Key players for
more » ... LRP5-mediated bone mass acquisition turn out to be different molecules with respect to the expressing tissue and action mode of these molecules. One is serotonin, a tryptophan metabolite that originates from duodenum, which acts as a negative regulator for bone formation. LRP5 suppresses serotonin biosynthesis by inhibiting the expression of tryptophan hydroxylase 1 in the gut. The other is sclerostin, an osteocyteproducing antagonist for LRP5 signaling. Here is a summary of recent findings about these two molecules, providing a chance to speculate new avenues in the LRP5-mediated bone mass acquisition.
doi:10.11005/kjbm.2012.19.1.1 fatcat:254dr5xszrds3flrgf2ylonz7a