Bone Mineralization and Regulation of Phosphate Homeostasis.

The physiological process of biomineralization (calcification) that occurs in bone tissue takes place throughout an individual's life. Complex biological systems carefully orchestrating crosstalk between skeletal tissue and mineralization modulators include environmental and physiological factors acting as promoters or inhibitors. They consist of local mineralization promoters synthesized by osteoblasts, the phosphatases, namely, tissue-nonspecific alkaline phosphatase (TNAP) and phosphatase orphan 1 (PHOSPHO1). The local inhibitors are produced by osteoblasts and osteocytes and include inorganic pyrophosphate (PPi) and organic non-collagenous proteins or peptides of the extracellular matrix, such as osteopontin. While these modulators act in a paracrine/autocrine manner, locally synthesized fibroblast growth factor 23 (FGF23) regulates systemic phosphate levels by creating bone-kidney-parathyroid feedback loops. Locally, the active role in regulation of mineralization and phosphate homeostasis is played by inorganic forms of phosphate itself, and in particular the Pi/PPi ratio. The upper control of this ratio is mediated by circulating effects of FGF23 on phosphate homeostasis. Bone cell products allow bone to play an active role in coordinating its mineralization with total systemic phosphate regulation. [ABSTRACT FROM AUTHOR]