Vitamin D compounds exert anti-apoptotic effects in human osteosarcoma cells in vitro

Several studies have demonstrated that vitamin D regulates growth and diffe rentiation in bone cells in vitro. In addition, in vivo studies have shown that vitamin D stimulates bone formation, increases the number of osteoblas t precursor cells and prevents bone mineral loss. These observations indica te that vitamin D mag; have anabolic effects on bone, and thus therapeutic potential in the treatment of osteoporosis. However, little is known about the effects of vitamin D on apoptosis in bone cells and about the contribut ion of this process to the effect of vitamin D on bone mineral loss. To inv estigate this aspect in more detail, we studied the effect of 1 alpha ,25(O H)(2)D,(3) and a series of analogues on apoptosis in human osteosarcoma cel ls. No significant induction of apoptosis was observed with any of the comp ounds after a 5 day treatment period. In contrast, some of the analogues sh owed a tendency to protect the cells from undergoing apoptosis. This anti-a poptotic effect of vitamin D was further confirmed by the ability of 1 alph a ,1.25(OH)(2)D-3 to suppress camptothecin- and staurosporin-induced DNA fr agmentation in the cells. In cultures treated simultaneously with 1 alpha , 25(OH)(2)D-3 in combination with camptothecin or staurosporin. the level of DNA Fragmentation was markedly reduced compared with cultures treated with camptothecin or staurosporin alone. On the basis of the present results it is therefore concluded that vitamin D displays anti-apoptotic effects in h uman osteoblast-like osteosarcoma cells in vitro. This observation suggests that besides regulating growth and differentiation, vitamin D exerts its a nabolic effects on bone by protecting osteoblastic cells from undergoing ap optosis. (C) 2001 Elsevier Science Ltd. All rights reserved.