Characteristics and regulation of Pi transport in osteogenic cells for bone metabolism.

Inorganic phosphate (Pi) is an essential element in the development of osteogenic cells. The translocation of Pi from the systemic to the skeletal extracellular compartment appears to be an important function of osteoblastic cells. The plasma membrane of osteogenic cells is endowed with a sodium-dependent Pi transport system that is regulated by osteotropic factors such as parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF) and fluoride. A similar Pi transport system has been recently identified in matrix vesicles derived from the plasma membrane of osteogenic cells, such as epiphyseal chondrocytes or osteoblastic cells. Matrix vesicles are extracellular structures which are considered to play an important role in endochondral and membranous calcification. Pi transport appears to be the driving force responsible for the accumulation of mineral inside the matrix vesicles and thereby can be considered as a pivotal determinant in the induction of the calcification process. Furthermore, modulation of the activity of the Pi transport at the level of the plasma membrane of osteogenic cells by osteotropic factors is transferred to the matrix vesicles derived from these cells. This notion implies that hormonal and other environmental factors, such as Pi itself and calcium, which have a direct impact on the Pi transport activity of osteogenic cells can also influence the capacity of the matrix vesicles to initiate the mineralization of the bone matrix. The cellular mechanisms involved in the regulation of Pi transport by osteotropic factors have been recently investigated. For the PTH/PTHrP regulatory effect, cAMP appears to be the main mediator and the response does not require the de novo synthesis of proteins. For the effects of IGF-1, PDGF and fluoride, tyrosine phosphorylation processes are involved and responses are dependent upon the de novo synthesis of proteins. The molecules responsible for activation of these signaling pathways are currently under investigation. Such an investigation may improve our understanding of the mechanisms underlying the differentiation processes of osteogenesis such as the calcification of the extracellular matrix.