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 sk eletal extracellular compartment appears to be an important function o f osteoblastic cells. The plasma membrane of osteogenic cells is endow ed with a sodium-dependent Pi transport system that is regulated by os teotropic factors such as parathyroid hormone (PTH), parathyroid hormo ne-related protein (PTHrP), insulin-like growth factor-1 (IGF-1), plat elet-derived growth factor (PDGF) and fluoride. A similar Pi transport system has been recently identified in matrix vesicles derived from t he plasma membrane of osteogenic cells, such as epiphyseal chondrocyte s or osteoblastic cells. Matrix vesicles are extracellular structures which are considered to play an important role in endochondral and mem branous calcification. Pi transport appears to be the driving force re sponsible for the accumulation of mineral inside the matrix vesicles, and thereby can be considered as a pivotal determinant in the inductio n of the calcification process. Furthermore, modulation of the activit y of the Pi transport at the Level of the plasma membrane of osteogeni c cells by osteotropic factors is transfered to the matrix vesicles de rived from these cells. This notion implies that hormonal and other en vironmental factors, such as Pi itself and calcium, which have a direc t impact on the Pi transport activity of osteogenic cells can also inf luence the capacity of the matrix vesicles to initiate the mineralizat ion of the bone matrix. The cellular mechanisms involved in the regula tion of Pi transport by osteotropic factors have been recently investi gated. For the PTH/PTHrP regulatory effect, cAMP appears to be the mai n mediator and the response does not require the de novo synthesis of proteins. For the effects of ICF-I, PDGF and fluoride, tyrosine phosph orylation processes are involved and responses are dependent upon the de novo synthesis of proteins. The molecules responsible for activatio n of these signaling pathways are currently under investigation. Such an investigation may improve our understanding of the mechanisms under lying the differentiation processes of osteogenesis such as the calcif ication of the extracellular matrix.