title: Fluoride inhibits the response of bone cells to mechanical loading.
abstract: The response of bone cells to mechanical loading is mediated by the cytoskeleton. Since the bone anabolic agent fluoride disrupts the cytoskeleton, we investigated whether fluoride affects the response of bone cells to mechanical loading, and whether this is cytoskeleton mediated. The mechano-response of osteoblasts was assessed in vitro by measuring pulsating fluid flow-induced nitric oxide (NO) production. Osteocyte shape was determined in hamster mandibles in vivo as parameter of osteocyte mechanosensitivity. Pulsating fluid flow (0.7 ± 0.3 Pa, 5 Hz) stimulated NO production by 8-fold within 5 min. NaF (10-50 μM) inhibited pulsating fluid flow-stimulated NO production after 10 min, and decreased F-actin content by ~3-fold. Fluid flow-induced NO response was also inhibited after F-actin disruption by cytochalasin B. NaF treatment resulted in more elongated, smaller osteocytes in interdental bone in vivo. Our results suggest that fluoride inhibits the mechano-response of bone cells, which might occur via cytoskeletal changes. Since decreased mechanosensitivity reduces bone mass, the reported anabolic effect of fluoride on bone mass in vivo is likely mediated by other factors than changed bone cell mechanosensitivity.
authors.affiliation: Department of Oral Cell Biology, ACTA-VU University Amsterdam, Research Institute MOVE, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands.
authors.forename: Hubertine M E
authors.initials: HM
authors.lastname: Willems
authors.forename: Ellen G H M
authors.initials: EG
authors.lastname: van den Heuvel
authors.forename: Seb
authors.initials: S
authors.lastname: Castelein
authors.forename: Joost Keverling
authors.initials: JK
authors.lastname: Buisman
authors.forename: Antonius L J J
authors.initials: AL
authors.lastname: Bronckers
authors.forename: Astrid D
authors.initials: AD
authors.lastname: Bakker
authors.forename: Jenneke
authors.initials: J
authors.lastname: Klein-Nulend
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000032:analysis / Q000187:drug effects; D000818:Animals; D001696:Biomechanical Phenomena; D002327:Cariostatic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D048430:Cell Shape / Q000187:drug effects; D006224:Cricetinae; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D005459:Fluorides / Q000494:pharmacology*; D057446:Hydrodynamics; D008334:Mandible / Q000166:cytology; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010011:Osteocytes / Q000187:drug effects*; D011673:Pulsatile Flow; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D000199:Actins; D002327:Cariostatic Agents; D009569:Nitric Oxide; D003571:Cytochalasin B; D005459:Fluorides