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The sphingosine-1-phosphate receptor 1 binding molecule FTY720 inhibits osteoclast formation in rats with ligature-induced periodontitis

 D.-E. Lee  ;  J.-H. Kim  ;  S.-H. Choi  ;  J.-H. Cha  ;  E.-J. Bak  ;  Y.-J. Yoo 
 JOURNAL OF PERIODONTAL RESEARCH, Vol.52(1) : 33-41, 2017 
Journal Title
Issue Date
S1PR1 ; osteoclast ; periodontitis
BACKGROUND AND 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. MATERIAL AND 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). CONCLUSION: 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.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Periodontics (치주과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ji Hye(김지혜)
Yoo, Yun Jung(유윤정) ORCID logo https://orcid.org/0000-0002-0045-9597
Cha, Jung Heon(차정헌) ORCID logo https://orcid.org/0000-0002-9385-2653
Choi, Seong Ho(최성호) ORCID logo https://orcid.org/0000-0001-6704-6124
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