title: Involvement of toll-like receptor 2 and 4 in association between dyslipidemia and osteoclast differentiation in apolipoprotein E deficient rat periodontium.
abstract: BACKGROUND
  Dyslipidemia increases circulating levels of oxidized low-density lipoprotein (OxLDL) and this may induce alveolar bone loss through toll-like receptor (TLR) 2 and 4. The purpose of this study was to investigate the effects of dyslipidemia on osteoclast differentiation associated with TLR2 and TLR4 in periodontal tissues using a rat dyslipidemia (apolipoprotein E deficient) model.
  
  
  METHODS
  Levels of plasma OxLDL, and the cholesterol and phospholipid profiles in plasma lipoproteins were compared between apolipoprotein E-deficient rats (16-week-old males) and wild-type (control) rats. In the periodontal tissue, we evaluated the changes in TLR2, TLR4, receptor activator of nuclear factor kappa B ligand (RANKL) and tartrate resistant acid phosphatase (TRAP) expression.
  
  
  RESULTS
  Apolipoprotein E-deficient rats showed higher plasma levels of OxLDL than control rats (p<0.05), with higher plasma levels of total cholesterol (p<0.05) and LDL-cholesterol (p<0.05) and lower plasma levels of high-density lipoprotein cholesterol (p<0.05). Their periodontal tissue also exhibited a higher ratio of RANKL-positive cells and a higher number of TRAP-positive osteoclasts than control rats (p<0.05). Furthermore, periodontal gene expression of TLR2, TLR4 and RANKL was higher in apolipoprotein E-deficient rats than in control rats (p<0.05).
  
  
  CONCLUSIONS
  These findings underscore the important role for TLR2 and TLR4 in mediating the osteoclast differentiation on alveolar bone response to dyslipidemia.
authors.affiliation: Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, 700-8558, Okayama, Kita-ku, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tomofuji
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ekuni
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Azuma
authors.forename: Koichiro
authors.initials: K
authors.lastname: Irie
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Endo
authors.forename: Kenta
authors.initials: K
authors.lastname: Kasuyama
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoneda
authors.forename: Manabu
authors.initials: M
authors.lastname: Morita
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D016301:Alveolar Bone Loss / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D002454:Cell Differentiation; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010519:Periodontium / Q000378:metabolism* / Q000473:pathology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D015398:Signal Transduction; D000071681:Tartrate-Resistant Acid Phosphatase; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007527:Isoenzymes; D008077:Lipoproteins, LDL; D053245:RANK Ligand; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase