Calcitonin promotes osteoclast survival in vitro.
Inactivation of resorbing osteoclasts by calcitonin is associated with typical morphological changes and alteration of the specific organization of osteoclast cytoskeleton. Here we show that calcitonin also promotes the survival of rat osteoclasts in vitro, cultured either on glass or bone, by delaying the onset of apoptosis. Parathyroid hormone had no effect on osteoclasts cultured on glass but it slightly increased apoptosis index of osteoclasts cultured on bone. Calcitonin was also able to rescue osteoclasts in calvarial explant cultures. The survival effect of calcitonin was mimicked by dibutyryl cAMP and could not be blocked by various metabolic inhibitors known to affect the apoptotic pathway. However, clodronate-induced apoptosis of osteoclasts could not be reversed by calcitonin and neither could calcitonin rescue osteoclasts already committed to apoptosis. It did not alter the distribution of Bcl-2 in osteoclasts. Our results show that at least in vitro calcitonin protects osteoclasts from apoptosis and suggest that it regulates the onset of apoptosis.
Selander
K S
KS
Department of Anatomy and Biocenter Oulu, University of Oulu, Finland. selander@phoenix.oulu.fi
Härkönen
P L
PL
Valve
E
E
Mönkkönen
J
J
Hannuniemi
R
R
Väänänen
H K
HK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004002:Clodronic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D010010:Osteoclasts / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats
D002257:Carbonic Anhydrase Inhibitors; D004791:Enzyme Inhibitors; D010281:Parathyroid Hormone; D019253:Proto-Oncogene Proteins c-bcl-2; D004002:Clodronic Acid; D003994:Bucladesine; D002116:Calcitonin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C