1alpha,25(OH)2-vitamin D3 membrane-initiated calcium signaling modulates exocytosis and cell survival.
J Steroid Biochem Mol Biol
; 103(3-5): 457-61, 2007 Mar.
Article
en En
| MEDLINE
| ID: mdl-17208437
1alpha,25(OH)(2)-vitamin D(3) (1,25D) is considered a bone anabolic hormone. 1,25D actions leading to bone formation involve gene transactivation, on one hand, and modulation of cytoplasmic signaling, on the other. In both cases, a functional vitamin D receptor (VDR) appears to be required. Here we study 1,25D-stimulated calcium signaling that initiates at the cell membrane and leads to exocytosis of bone materials and increased osteoblast survival. We found that rapid 1,25D-induction of exocytosis couples to cytoplasmic calcium increase in osteoblastic ROS 17/2.8 cells. In addition, we found that elevation of cytoplasmic calcium concentration is involved in 1,25D anti-apoptotic effects via Akt activation in ROS 17/2.8 cells and non-osteoblastic CV-1 cells. In both cases, 1,25D-stimulated elevation of intracellular calcium is due in part to activation of L-type Ca(2+) channels. We conclude that 1,25D bone anabolic effects that involve increased intracellular Ca(2+) concentration in osteoblasts can be explained at two levels. At the single-cell level, 1,25D promotes Ca(2+)-dependent exocytotic activities. At the tissue level, 1,25D protects osteoblasts from apoptosis via a Ca(2+)-dependent Akt pathway. Our studies contribute to the understanding of the molecular basis of bone diseases characterized by decreased bone formation and mineralization.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcitriol
/
Señalización del Calcio
/
Exocitosis
Límite:
Animals
Idioma:
En
Revista:
J Steroid Biochem Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido