P-I TRANSPORT REGULATION BY CHICKEN GROWTH-PLATE CHONDROCYTES

Inorganic phosphate (P-i) is a key element for the growth and mineralization of the epiphyseal cartilage. In this study, the characteristics of the transport of P-i in growth plate chondrocytes have been determined using primary cultures of chicken growth plate cartilage cells. The uptake of P-i was significantly increased in the presence of extracellular sodium. The kinetic parameters of the saturable sodium-dependent P-i transport (NaPiT) were determined. The Michaelis constant for P-i was 0.443 +/- 0.095 mM, and the concentration of sodium with which half-maximal P-i transport was observed was 48.0 +/- 8.7 mM. Stoichiometric analysis suggested that more than one sodium ion was cotransported with each P-i molecule. NaPiT was sensitive to inhibition by P-i analogues such as phosphonoformic acid and arsenate. These data strongly suggest that P-i uptake by chicken growth plate chondrocytes is a carrier-mediated process driven by the transmembrane electrochemical gradient of sodium. Two important regulators of biosynthetic activities of growth plate chondrocytes, insulin-like growth factor I (IGF-I) and parathyroid hormone (PTH), selectively regulated P-i transport. With IGF-I, maximal stimulation (117 +/- 7% above control) was observed at doses >5 nM, with an half-maximal effective concentration of 0.46 +/- 0.18 nM. A significant effect was observed after 1 h of exposure and was maintained for up to 24 h. PTH increased P-i transport with a biphasic dose-response curve. The change in NaPiT was transient, being maximally observed after 8 h (58 +/- 8%) and unexpressed after 24 h. In conclusion, P-i transport in growth plate chondrocytes is a carrier-mediated process that is selectively stimulated by IGF-I and PTH, two physiological regulators of growth plate chondrocyte development.