CALCITONIN INHIBITS OSTEOPONTIN MESSENGER-RNA EXPRESSION IN ISOLATED RABBIT OSTEOCLASTS

Recent evidence indicates that osteopontin (Opn), one of the bone matr ix proteins, plays an important role in the attachment of osteoclasts to bone matrix. Besides being elaborated by osteoblasts, this protein is also produced by osteoclasts. The present study was performed to ex amine the effect of calcitonin (CT) on Opn mRNA expression of isolated rabbit osteoclasis and to clarify the second messenger signaling of t his effect. Eel CT inhibited Opn mRNA expression as well as bone-resor bing activity of isolated rabbit osteoclasts. Eel CT caused a transien t increase in intracellular calcium followed by a sustained increase a s well as an increase in cAMP production in these cells. Dibutyryl-cAM P (10(-4) M) and Sp-cAMPS (10(-4) M), an activator of cAMP-dependent p rotein kinase (PKA), as well as A23187 (10(-7) M), a calcium ionophore , and phorbol myristate acetate (10(-7) M), an activator of protein ki nase C (PKC), caused a significant inhibition of Opn mRNA expression, and suppressed tone-resorbing activity of isolated osteoclasis. The pr esent study is the first to demonstrate that CT inhibits Opn mRNA expr ession in isolated rabbit osteoclasis, presumably through the activati on of PKA and calcium/PKC pathways, by which the bone-resorbing activi ty might be attenuated subsequently.