title: The sphingosine-1-phosphate receptor 1 binding molecule FTY720 inhibits osteoclast formation in rats with ligature-induced periodontitis.
abstract: OBJECTIVE
  Osteoclast precursors (OPs) re-migrate from the bone surface into blood vessels through sphingosine-1-phosphate receptor 1 (S1PR1) expression. T cells also express S1PR1, mediating their migration from the lymph nodes into blood vessels. OP and T-cell migration are one of the sequential steps related to osteoclast formation. To characterize the role of S1PR1 in osteoclast formation induced by periodontitis, we investigated the effect of S1PR1-binding molecule FTY720 (FTY) on the number of OPs and T cells in periodontal tissue and peripheral blood of rats with ligature-induced periodontitis.
  
  
  METHODS
  Rats were divided into four groups; control (Con), FTY, periodontitis (Peri), and periodontitis+FTY (Peri+FTY) groups. Ligatures were placed around the first molars in the left and right mandibles. The rats were intraperitoneally injected with vehicle or 3 mg/kg FTY daily until they were killed. The number of osteoclasts and cluster of differentiation (CD)11b, CD3 and receptor activator of NF-κB ligand (RANKL)-positive cells in first molar furcation were counted by tartrate-resistant acid phosphatase or immunohistochemistry staining. The number of CD11b- and CD3-positive cells in peripheral blood was estimated by flow cytometry.
  
  
  RESULTS
  The number of osteoclasts in the Peri group was higher than Con, Peri+FTY and FTY groups (p < 0.05) and CD11b, CD3 and RANKL-positive cells were also higher in the Peri group than other groups in furcation (p < 0.05). While CD11b-positive cells in furcation of the Peri+FTY group were lower than the Peri group (p < 0.05), they were higher in peripheral blood (p < 0.05). Dissimilar to CD11b-positive cells, CD3-positive cells in the Peri+FTY group were lower in peripheral blood as well as furcation than the Peri group (p < 0.05). RANKL-positive cells in furcation of the Peri+FTY group were also lower than Peri group (p < 0.05).
  
  
  CONCLUSIONS
  These results indicate that FTY may facilitate re-migration of OPs from the alveolar bone surface into blood vessels, blocking T-cell migration from the lymph nodes into blood vessels and subsequently reducing osteoclast formation induced by periodontitis. This suggests that S1PR1-S1P binding may play a role in osteoclast formation of periodontitis by modulating OP and T-cell migration.
authors.affiliation: Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea.|Brain Korea 21 Plus Project, Yonsei University College of Dentistry, Seoul, South Korea.
authors.forename: D-E
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea.|Brain Korea 21 Plus Project, Yonsei University College of Dentistry, Seoul, South Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Periodontology, Research Institute for Periodontal Regeneration, Yonsei University College of Dentistry, Seoul, South Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea.|Brain Korea 21 Plus Project, Yonsei University College of Dentistry, Seoul, South Korea.|Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Cha
authors.affiliation: Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea.
authors.forename: E-J
authors.initials: EJ
authors.lastname: Bak
authors.affiliation: Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Yoo
mesh_terms: D016301:Alveolar Bone Loss / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology*; D005434:Flow Cytometry; D017823:Furcation Defects / Q000378:metabolism / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: S1PR1; osteoclast; periodontitis