title: Compressive force induces osteoclast differentiation via prostaglandin E(2) production in MC3T3-E1 cells.
abstract: In orthodontic tooth movement, prostaglandin E(2) (PGE(2)) released from osteoblasts can alter the normal process of bone remodeling. We previously showed that compressive force (CF) controls bone formation by stimulating the production of PGE(2) and Ep2 and/or Ep4 receptors in osteoblasts. The present study was undertaken to examine the effect of CF on the production of PGE(2), cyclooxygenase-2 (COX-2), macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) using osteoblastic MC3T3-E1 cells and to examine the indirect effect of CF on osteoclast differentiation using RAW264.7 cells as osteoclast precursors. MC3T3-E1 cells were cultured with or without continuous CF (1.0 or 3.0 g/cm(2)) for 24 hr, and PGE(2) production was determined using ELISA. The expression of COX-2, M-CSF, RANKL, and OPG genes and proteins was determined using real-time PCR and ELISA, respectively. Osteoclast differentiation was estimated using tartrate-resistant acid phosphatase (TRAP) staining of RAW 264.7 cells cultured for 10 days with conditioned medium from CF-treated MC3T3-E1 cells and soluble RANKL. As CF increased, PGE(2) production and the expression of COX-2, M-CSF, and RANKL increased, whereas OPG expression decreased. The number of TRAP-positive cells increased as CF increased. Celecoxib, a specific inhibitor of COX-2, blocked the stimulatory effect of CF on TRAP staining and the production of PGE(2), M-CSF, RANKL, and OPG. These results suggest that CF induces osteoclast differentiation by increasing M-CSF production and decreasing OPG production via PGE(2) in osteoblasts.
authors.affiliation: Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Sanuki
authors.forename: Chieko
authors.initials: C
authors.lastname: Shionome
authors.forename: Akiko
authors.initials: A
authors.lastname: Kuwabara
authors.forename: Narihiro
authors.initials: N
authors.lastname: Mitsui
authors.forename: Yuki
authors.initials: Y
authors.lastname: Koyama
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Masao
authors.initials: M
authors.lastname: Maeno
mesh_terms: D016475:3T3 Cells; D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000068579:Celecoxib; D002454:Cell Differentiation / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012886:Skull / Q000166:cytology; D013314:Stress, Mechanical; D013449:Sulfonamides / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D017077:Culture Media, Conditioned; D052246:Cyclooxygenase 2 Inhibitors; D007527:Isoenzymes; D053244:Osteoprotegerin; D011720:Pyrazoles; D053245:RANK Ligand; D013449:Sulfonamides; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D000068579:Celecoxib; D015232:Dinoprostone