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Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis.

 Ji-Hye Kim  ;  Ae Ri Kim  ;  Yun Hui Choi  ;  Sungil Jang  ;  Gye-Hyeong Woo  ;  Jeong-Heon Cha  ;  Eun-Jung Bak  ;  Yun-Jung Yoo 
 PLOS ONE, Vol.12(12) : e0189702, 2017 
Journal Title
Issue Date
Alveolar Bone Loss ; Animals ; Bone Morphogenetic Proteins/metabolism* ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/metabolism* ; Genetic Markers ; Immunohistochemistry ; Infliximab/pharmacology* ; Male ; Osteocytes/drug effects* ; Osteocytes/metabolism ; Periodontitis/complications ; Periodontitis/metabolism* ; RANK Ligand/metabolism* ; Rats ; Rats, Inbred F344 ; Tumor Necrosis Factor-alpha/antagonists & inhibitors*
Type 1 diabetes with periodontitis shows elevated TNF-α expression. Tumor necrosis factor (TNF)-α stimulates the expression of receptor activator of nuclear factor-κB ligand (RANKL) and sclerostin. The objective of this study was to determine the effect of TNF-α expression of osteocytic RANKL and sclerostin in type 1 diabetes rats with periodontitis using infliximab (IFX), a TNF-α antagonist. Rats were divided into two timepoint groups: day 3 and day 20. Each timepoint group was then divided into four subgroups: 1) control (C, n = 6 for each time point); 2) periodontitis (P, n = 6 for each time point); 3) diabetes with periodontitis (DP, n = 8 for each time point); and 4) diabetes with periodontitis treated with IFX (DP+IFX, n = 8 for each time point). To induce type 1 diabetes, rats were injected with streptozotocin (50 mg/kg dissolved in 0.1 M citrate buffer). Periodontitis was then induced by ligature of the mandibular first molars at day 7 after STZ injection (day 0). IFX was administered once for the 3 day group (on day 0) and twice for the 20 day group (on days 7 and 14). The DP group showed greater alveolar bone loss than the P group on day 20 (P = 0.020). On day 3, higher osteoclast formation and RANKL-positive osteocytes in P group (P = 0.000 and P = 0.011, respectively) and DP group (P = 0.006 and P = 0.017, respectively) than those in C group were observed. However, there was no significant difference in osteoclast formation or RANKL-positive osteocytes between P and DP groups. The DP+IFX group exhibited lower alveolar bone loss (P = 0.041), osteoclast formation (P = 0.019), and RANKL-positive osteocytes (P = 0.009) than that of the DP group. On day 20, DP group showed a lower osteoid area (P = 0.001) and more sclerostin-positive osteocytes (P = 0.000) than P group. On days 3 and 20, the DP+IFX group showed more osteoid area (P = 0.048 and 0.040, respectively) but lower sclerostin-positive osteocytes (both P = 0.000) than DP group. Taken together, these results suggest that TNF-α antagonist can diminish osteocytic RANKL/sclerostin expression and osteoclast formation, eventually recovering osteoid formation. Therefore, TNF-α might mediate alveolar bone loss via inducing expression of osteocytic RANKL and sclerostin in type 1 diabetes rats with periodontitis.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Yoo, Yun Jung(유윤정) ORCID logo https://orcid.org/0000-0002-0045-9597
Jang, Sungil(장성일) ORCID logo https://orcid.org/0000-0001-6144-6899
Cha, Jung Heon(차정헌) ORCID logo https://orcid.org/0000-0002-9385-2653
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