Calcitonin in human odontoclasts regulates root resorption activity via protein kinase A.
Calcitonin is a known inhibitor of osteoclastic bone resorption, but it remains uncertain whether calcitonin also regulates human odontoclastic activity, particularly during the physiological process of root resorption. In this study, we examined the expression of calcitonin receptors in human odontoclasts and the effect of calcitonin on root resorption, using immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Actin-ring formation was used to assess cytostructural changes during resorption activity. Our results show that calcitonin receptors are expressed in human odontoclasts freshly isolated from deciduous teeth of the periodontal region. Calcitonin inhibited actin-ring formation and resorption activity. This calcitonin-induced inhibition was mimicked by forskolin and dibutyryl-adenosine 3',5'-cyclic monophosphate (db-cAMP), which are protein kinase A (PKA) activators, but not by phorbol 12-myristate 13-acetate, a protein kinase C activator. Pretreatment with adenosine 3',5'-cyclic monophosphothioate Rp diastereomer (Rp-cAMPS), a PKA inhibitor, suppressed the calcitonin-induced inhibition of actin-ring formation. These results indicate that calcitonin receptor activation suppresses odontoclastic root resorption via PKA, a signaling pathway different from that in human osteoclasts.
Takada
Keisuke
K
Department of Oral Growth and Development, Fukuoka Dental College, Fukuoka, Japan.
Kajiya
Hiroshi
H
Fukushima
Hidefumi
H
Okamoto
Fujio
F
Motokawa
Wataru
W
Okabe
Koji
K
D000135:Acid Phosphatase / Q000378:metabolism; D000199:Actins / Q000032:analysis / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008858:Microscopy, Phase-Contrast; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism; D018003:Receptors, Calcitonin / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012391:Root Resorption / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000071681:Tartrate-Resistant Acid Phosphatase; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014094:Tooth, Deciduous / Q000033:anatomy & histology / Q000201:enzymology
D000199:Actins; D007527:Isoenzymes; D018003:Receptors, Calcitonin; D013873:Thionucleotides; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D003994:Bucladesine; D002116:Calcitonin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D013755:Tetradecanoylphorbol Acetate