화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.285, No.5, 1226-1231, 2001
Extracellular NAD(+) induces calcium signaling and apoptosis in human osteoblastic cells
ADP-ribosyl cyclase/CD38 is a bifunctional enzyme that catalyzes at its ectocellular domain the synthesis from NAD(+) (cyclase) and the hydrolysis (hydrolase) of the calcium-mobilizing second messenger cyclic ADP ribose (cADPR). Furthermore, CD38 mediates cADPR influx inside a number of cells, thereby inducing Ca2+ mobilization. Intracellularly, cADPR releases Ca2+ from ryanodine-sensitive pools, thus activating several Ca2+-dependent functions. Among these, the inhibition of osteoclastic-mediated bone resorption has been demonstrated. We found that HOBIT human osteoblastic cells display ADP-ribosyl cyclase activity and we examined the effects of CD38 stimulation on osteoblasts function. Extracellular NAD+ induced elevation of cytosolic calcium due to both Ca2+ influx from the extracellular medium and Ca2+ release from ryanodine-sensitive intracellular stores. Culturing these cells in the presence of NAD(+) caused a complete growth arrest with a time-dependent decrease of cell number and the appearance of apoptotic nuclei. The first changes could be observed after 24 h of treatment and became fully evident after 72-96 h. We propose a role of extracellular NAD+ in bone homeostatic control.