TGF-beta1 calcium signaling in osteoblasts.
Transforming growth factor-beta1 (TGF-beta1) action is known to be initiated by its binding to multiple cell surface receptors containing serine/threonine kinase domains that act to stimulate a cascade of signaling events in a variety of cell types. We have previously shown that TGF-beta1 and BMP-2 treatment of primary human osteoblasts (HOBs) enhances cell-substrate adhesion. In this report, we demonstrate that TGF-beta1 elicits a rapid, transient, and oscillatory rise in the intracellular Ca(2+) concentration, [Ca(2+)](i), that is necessary for enhancement of cell adhesion in HOBs but does not alter the phosphorylation state of Smad proteins. This rise in [Ca(2+)](i) in HOB is not observed in the absence of extracellular calcium or when the cells are treated with the L-type Ca(2+) channel blocker, nifedipine, but is stimulated upon treatment with the L-type Ca(2+) channel agonist, Bay K 8644, or under high K(+) conditions. The rise in [Ca(2+)](i) is severely attenuated after treatment of the cells with thapsigargin, a selective endoplasmic reticulum Ca(2+) pump inhibitor. TGF-beta1 enhancement of HOB adhesion to tissue culture polystyrene is also inhibited in cells treated with nifedipine. These data suggest that intracellular Ca(2+) signaling is an important second messenger of the TGF-beta1 signal transduction pathway in osteoblast function.
Nesti
Leon J
LJ
Department of Orthopaedics and Rehabilitation, Walter Reed Army Medical Center, Washington, DC 20307, USA.
Caterson
E J
EJ
Li
Wan-Ju
WJ
Chang
Richard
R
McCann
Thane D
TD
Hoek
Jan B
JB
Tuan
Rocky S
RS
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D009543:Nifedipine / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D019284:Thapsigargin / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D053773:Transforming Growth Factor beta1; D019284:Thapsigargin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium