Abstract
Fibroblasts isolated from jaw cysts expressed calcium-sensing receptor (CasR). In the fibroblasts elevated extracellular Ca(2+) ([Ca(2+)](o)) increased fluo-3 fluorescence intensity, and the production of inositol(1,4,5)trisphosphate and active protein kinase C. Phospholipase C inhibitor U-73122 attenuated the Ca(2+)-induced increase in fluo-3 fluorescence intensity. Elevated [Ca(2+)](o) enhanced the expression of cyclooxygenase-2 (COX-2) mRNA and protein, and the secretion of prostaglandin E(2) in the fibroblasts. CasR activator neomycin also increased the expression of COX-2 mRNA, and U-73122 attenuated the Ca(2+)-induced expression of COX-2 mRNA. Elevated [Ca(2+)](o)-induced phosphorylation of extracellular signal-regulated protein kinase-1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK), and U-73122 inhibited the Ca(2+)-induced phosphorylation. The inhibitors for each kinase, PD98059, SB203580, and SP600125, attenuated the Ca(2+)-induced expression of COX-2 mRNA. These results suggest that in jaw cyst fibroblasts elevated extracellular Ca(2+) may enhance COX-2 expression via the activation of ERK1/2, p38 MAPK, and JNK through CasR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anthracenes / pharmacology
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Bone and Bones / cytology*
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Bone and Bones / drug effects
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Bone and Bones / enzymology
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Calcium / metabolism*
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Calcium Signaling
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Cations, Divalent / metabolism
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism*
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Dinoprostone / metabolism
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Estrenes / pharmacology
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Fibroblasts / drug effects
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Fibroblasts / enzymology*
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Flavonoids / pharmacology
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Humans
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Imidazoles / pharmacology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Phosphorylation
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Protein Kinase Inhibitors / pharmacology
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Pyridines / pharmacology
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Pyrrolidinones / pharmacology
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RNA, Messenger / metabolism
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Receptors, Calcium-Sensing / genetics
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Receptors, Calcium-Sensing / metabolism*
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Type C Phospholipases / antagonists & inhibitors
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Type C Phospholipases / metabolism
Substances
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Anthracenes
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Cations, Divalent
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Estrenes
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Flavonoids
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Imidazoles
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Protein Kinase Inhibitors
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Pyridines
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Pyrrolidinones
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RNA, Messenger
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Receptors, Calcium-Sensing
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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pyrazolanthrone
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Cyclooxygenase 2
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Mitogen-Activated Protein Kinases
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Type C Phospholipases
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Dinoprostone
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Calcium