Korean J Bone Metab.  2012 May;19(1):1-9. 10.11005/kjbm.2012.19.1.1.

New Avenues in the LRP5-mediated Bone Mass Acquisition

• Choi JY

• KMID: 1464230
• DOI: http://doi.org/10.11005/kjbm.2012.19.1.1

Abstract

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)beta-catenin signaling pathway using osteoblast-lineage specific Cre mice. Key players for 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 osteocyte-producing 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.

Keyword

Bone mass; LRP5; Sclerostin; Serotonin; Wnt signaling

MeSH Terms

Animals
Bone Diseases, Metabolic
Duodenum
Humans
Lipoproteins
Mice
Mitral Valve Prolapse
Myopia
Osteogenesis
Osteoporosis
Phenotype
Serotonin
Skin Diseases
Tryptophan
Tryptophan Hydroxylase
Lipoproteins
Mitral Valve Prolapse
Myopia
Serotonin
Skin Diseases
Tryptophan
Tryptophan Hydroxylase