| [ Summary ] |
While our understanding of the regulation of calcium homeostasis has significantly advanced, little has been known about the mechanisms by which phosphate homeostasis is controlled until recently. Studies on inherited diseases such as X-linked hypophosphatemic rickets (XLH) and autosomal dominant hypophosphatemic rickets (ADHR) or paraneoplastic syndromes such as oncogenic hypophosphatemic osteomalacia (OHO) that are associated with hypophosphatemia, phosphaturia and impaired ossification have led us to search for a phosphate lowering and calcification inhibiting circulating hormone-like factor. This factor is generically called “phosphatonin”. At the moment, three candidate molecules for phosphatonin have been identified, they are fibroblast growth factor 23 (FGF23), matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein-4 (sFRP-4). In this chapter, I will describe our current knowledge of the biological functions of these molecules in physiologic and pathologic conditions with a focus on the regulation of blood and urinary phosphate levels and hard tissue mineralization. It is certain that deepening our insights into the mechanism of phosphate homeostasis and skeletal calcification will allow us to study bone biology with new ideas and approaches. |