title: F-spondin inhibits migration and differentiation of osteoclastic precursors.
abstract: BACKGROUND
  Clinically, severe cemental resorption is a rare consequence of periodontitis, although alveolar bone resorption by osteoclasts is one of the main pathologic changes. F-spondin is a secreted neuronal glycoprotein that localizes to the cementum. F-spondin is among the cementum-specific factors in periodontal tissue that have been reported. However, the effects of F-spondin on osteoclastogenesis have not yet been established. We examined the effects of F-spondin on stages of osteoclastogenesis, migration, and differentiation in a mouse osteoclastic precursor model, RAW 264 cells.
  
  
  METHODS
  RAW 264 cells were treated with recombinant F-spondin. Macrophage colony stimulating factor (M-CSF)-induced cell migration was examined by migration assay performed with cell culture inserts. Osteoclastic differentiation was measured by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells.
  
  
  RESULTS
  In a transmigration assay, F-spondin significantly downregulated M-CSF-induced cell migration. Further, F-spondin significantly reduced the number of receptor activator of nuclear factor-kappa B ligand-induced TRAP-positive multinucleated cells. The receptor-associated protein, an antagonist of the low-density lipoprotein (LDL) receptor family, blocked the effects of F-spondin on M-CSF-induced migration. The suppressive effect of F-spondin on M-CSF-induced cell migration was blocked by knockdown of LDL receptor-related protein 8 (LRP8), a member of the LDL receptor family.
  
  
  CONCLUSIONS
  Our findings suggest that F-spondin downregulates recruitment to the root side of periodontal tissue via LRP8 and inhibits differentiation of osteoclastic precursors. It is suggested that F-spondin is essential to protect the root surface from resorption.
authors.affiliation: Promoting Office of Graduate Program for BioDental Education, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan. okhiroko@hiroshima-u.ac.jp
authors.forename: Hiroko
authors.initials: H
authors.lastname: Oka
authors.forename: Maya
authors.initials: M
authors.lastname: Mori
authors.forename: Hisae
authors.initials: H
authors.lastname: Kihara
mesh_terms: D016301:Alveolar Bone Loss / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003739:Dental Cementum / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000494:pharmacology / Q000502:physiology*; D055785:Gene Knockdown Techniques; D026502:LDL-Receptor Related Proteins / Q000235:genetics / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D008264:Macrophages / Q000166:cytology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D011973:Receptors, LDL / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins
chemical_list: D016326:Extracellular Matrix Proteins; C552523:F-spondin protein, mouse; D026502:LDL-Receptor Related Proteins; D053245:RANK Ligand; D011973:Receptors, LDL; D011994:Recombinant Proteins; C429104:SPON1 protein, human; C098773:low density lipoprotein receptor-related protein 8; D016173:Macrophage Colony-Stimulating Factor