Clodronate inhibits PGE(2) production in compressed periodontal ligament cells.
Periodontal ligament (PDL) cells play an essential role in orthodontic tooth movement. We recently reported that clodronate, a non-N-containing bisphosphonate, strongly inhibited tooth movement in rats, and thus could be a useful adjunct for orthodontic treatment. However, it is not clear how clodronate affects the responses of PDL cells to orthodontic force. In this study, we hypothesized that clodronate prevents the mechanical stress-induced production of prostaglandin E(2) (PGE(2)), interleukin-1beta (IL-1beta), and nitric oxide (NO) in human PDL cells. A compressive stimulus caused a striking increase in PGE(2) production, while the responses of IL-1beta and NO were less marked. Clodronate concentration-dependently inhibited the stress-induced production of PGE(2). Clodronate also strongly inhibited stress-induced gene expression for COX-2 and RANKL. These results suggest that the inhibitory effects of clodronate on tooth movement and osteoclasts may be due, at least in part, to the inhibition of COX-2-dependent PGE(2) production and RANKL expression in PDL cells.
Liu
L
L
Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Igarashi
K
K
Kanzaki
H
H
Chiba
M
M
Shinoda
H
H
Mitani
H
H
D000328:Adult; D000704:Analysis of Variance; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002478:Cells, Cultured; D004002:Clodronic Acid / Q000494:pharmacology*; D019245:Compressive Strength; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003799:Dental Stress Analysis; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014087:Tooth Movement Techniques
D050071:Bone Density Conservation Agents; D002352:Carrier Proteins; D052246:Cyclooxygenase 2 Inhibitors; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D004002:Clodronic Acid; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D015232:Dinoprostone