Evidence that protein kinase-A, calcium-calmodulin kinase and cytoskeletal proteins are involved in osteoclast retraction induced by calcitonin.
Calcitonin is a direct inhibitor of osteoclastic activity. Osteoclast retraction is readily induced by calcitonin and it is possible that calcitonin-induced inhibition of bone resorption is in part due to this effect. However, little is known of the mechanisms of this action. In these studies, we have investigated the intracellular signalling pathway of calcitonin-induced osteoclast retraction using cultures of freshly isolated rat osteoclasts. The spread area occupied by single Giemsa-stained rat osteoclasts was measured in vitro by a computer imaging analysis system and used as a quantitative parameter for calculating the degree of osteoclast retraction in response to various agents. Our results show that cAMP may be an important second messenger in the reaction of osteoclasts to calcitonin. Moreover, both protein kinase-A and calcium/calmodulin-dependent protein kinase are involved in the osteoclast retraction induced by this hormone, while cytoskeletal proteins are required for the process to occur.
Zheng
M H
MH
Department of Orthopaedics, University of Western Australia.
Wood
D J
DJ
Papadimitriou
J M
JM
Nicholson
G C
GC
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001862:Bone Resorption; D002116:Calcitonin / Q000494:pharmacology*; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology
D003598:Cytoskeletal Proteins; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D005576:Colforsin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002116:Calcitonin; D014700:Verapamil; D011494:Protein Kinases; D011493:Protein Kinase C; D010741:Phospholipases A; D010738:Type C Phospholipases; D011796:Quinacrine; D009355:Neomycin; D003078:Colchicine