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

• Published in: Journal of periodontal research 2017-02, Vol.52 (1), p.33-41
• Main Authors: Lee, D.‐E., Kim, J.‐H., Choi, S.‐H., Cha, J.‐H., Bak, E.‐J., Yoo, Y.‐J.
• Format: Article
• Language: English
• Subjects: Acid phosphatase (tartrate-resistant); Alveolar bone; Alveolar Bone Loss - metabolism; Animals; Blood vessels; CD11b antigen; CD3 antigen; Cell adhesion & migration; Cell migration; Dentistry; Disease Models, Animal; Fingolimod Hydrochloride - pharmacology; Flow Cytometry; FTY720; Furcation Defects - metabolism; Furcation Defects - pathology; Gum disease; Hemopoiesis; Immunohistochemistry; Immunosuppressive Agents - pharmacology; Ligation; Lymph nodes; Lymphatic system; Lymphocytes B; Lymphocytes T; Male; Mandible; Molars; NF-κB protein; osteoclast; Osteoclastogenesis; Osteoclasts; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoprogenitor cells; Periodontitis; Periodontitis - metabolism; Periodontitis - pathology; Peripheral blood; Rats; Rats, Sprague-Dawley; Rodents; S1PR1; T-Lymphocytes - metabolism; Teeth
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/jre.12366

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.