Reciprocal regulation by cyclic nucleotides of the differentiation of rat osteoblast-like cells and mineralization of nodules.
The effects of cAMP and cGMP on the differentiation of osteoblast-like cells derived from rat calvariae and on the formation of bone in vitro were studied. Continuous culture of osteoblast-like cells in the presence of 8-bromo-cyclic AMP (8-Br-cAMP) resulted in the dose-related inhibition both of the synthesis of cellular alkaline phosphatase (ALPase), which is known as a marker of osteoblastic differentiation, and of the formation of mineralized nodules, which is a model of the formation of bone in vitro. By contrast, 8-bromo-cyclic GMP (8-Br-cGMP) promoted the synthesis of ALPase and the formation of mineralized nodules. Northern blot analysis revealed that these cyclic nucleotides modulated the steady-state levels of mRNAs for ALPase and osteocalcin, a bone-matrix protein that is specifically produced by osteoblast. The present results indicate that cAMP and cGMP act reciprocally to regulate osteoblastic differentiation and the subsequent formation of mineralized nodules.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D015152:Blotting, Northern; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006706:Homeostasis; D007700:Kinetics; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000166:cytology*
D015415:Biomarkers; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D006152:Cyclic GMP