The zinc receptor is essential to maintain bone homeostasis and skeletal strength

Changes in bone mass and matrix composition are frequently found with bone diseases and may be associated with increased fracture risk. An extreme example is osteogenesis imperfecta (OI) a skeletal disease characterized by brittle bones. The brittle bones of OI are a result of impaired bone collagen deposition with abnormal mineralization. We show that the zinc receptor, ZnR/Gpr39, is required for normal bone matrix deposition by osteoblasts the bone building cells. Our analysis shows that ZnR/GPR39 deficiency in mice results in an osteogenesis imperfecta like phenotype with altered bone composition. These alterations weaken the bone material and make it more prone to resorption. On the molecular level we show that ZnR/Gpr39 regulates collagen half-life and its absence result in diminished collagen levels. Our data establish a link between the Zinc receptor collagen deposition and bone integrity and shed light on a novel molecular mechanism that maybe involved in the pathogenesis of OI.