title: Osteopontin is required for unloading-induced osteoclast recruitment and modulation of RANKL expression during tooth drift-associated bone remodeling, but not for super-eruption.
abstract: Unloading of teeth results in extensive alveolar bone remodeling, causing teeth to move in both vertical ("super-eruption") and horizontal direction ("drift"). In order to decipher the molecular mechanisms of unloading-induced bone remodeling during tooth movement, we focused on the role of osteopontin (OPN) in the un-opposed molar model, comparing wild-type (WT) and OPN-null mice. Our data indicated that OPN was not required for the continuous eruption of un-opposed teeth while OPN was necessary for the drift of teeth. OPN expression and osteoclast counts were greatly increased on alveolar bone surfaces facing the direction of the drift in WT mice, while osteoclast counts were diminished in OPN-/- mice. RANKL expression in the distal periodontal ligament of WT molars increased significantly by day 6 following unloading, while overall levels of RANKL expression were decreased in both WT and OPN-null mice. In vitro treatment of MC3T3 cells, WT BMCs and OPN-/- BMCs with recombinant OPN resulted in significantly increased RANKL expression in all three cell types. The PI3K and MEK/ERK pathway inhibitors Ly294002 and U0126 reduced RANKL expression levels in vitro. Treatment of BMCs and MC3T3 with OPN also resulted in increased ERK phosphorylation and reduced OPG levels. Together, our studies suggest that increased OPN expression during unloading-induced drifting of teeth enhances localized RANKL expression and osteoclast activity on drift-direction alveolar bone surfaces via extracellular matrix signaling pathways.
authors.affiliation: Department of Oral Biology, University of Illinois at Chicago, Chicago, IL, USA. cwalke2@uic.edu
authors.forename: Cameron G
authors.initials: CG
authors.lastname: Walker
authors.forename: Smit
authors.initials: S
authors.lastname: Dangaria
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Xianghong
authors.initials: X
authors.lastname: Luan
authors.forename: Thomas G H
authors.initials: TG
authors.lastname: Diekwisch
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008963:Molar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D053495:Osteopontin / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D053244:Osteoprotegerin / Q000378:metabolism; D010513:Periodontal Ligament / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D011859:Radiography; D014078:Tooth Eruption / Q000187:drug effects / Q000502:physiology*; D014085:Tooth Migration / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D053495:Osteopontin; D053244:Osteoprotegerin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D053245:RANK Ligand