Project 176423

Lay Abstract: Bones and teeth are hard tissues, the usual sites for physiologic mineral accumulation. These mineralized tissues protect the internal soft organs, help in locomotion, facilitate food processing and more importantly serve as a reservoir for essential mineral ions required for proper body functions. A poor hard tissue mineralization, as seen in rickets, might cause a serious health concern, while soft tissue mineralization in diseases like osteoarthritis is an undesirable event. The long-term goal of this proposal is to identify novel mechanisms regulating both soft and heard tissue mineralization. Towards this goal, I plan to characterize a mouse model, fro/fro, which shows a severely under-mineralized bones and teeth. Recently, a genetic mutation in this model has been identified. Smpd3, the gene mutated, codes for an enzyme involved in the metabolism of several fat-soluble molecules. I will investigate how Smpd3 function affects bone and tooth cells and if the abnormalities caused by the mutation can be reversed by pharmacological or genetic manipulations in the mutated mouse model. I believe, this work might provide clues to a novel mechanism regulating tissue mineralization. Unveiling such mechanisms should eventually identify new therapeutic targets and improve the management of human pathologic conditions related to bone and tooth mineralization defects.