Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis.
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 sc...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5730195?pdf=render |
| _version_ | 1818136399581282304 |
|---|---|
| author | Ji-Hye Kim Ae Ri Kim Yun Hui Choi Sungil Jang Gye-Hyeong Woo Jeong-Heon Cha Eun-Jung Bak Yun-Jung Yoo |
| author_facet | Ji-Hye Kim Ae Ri Kim Yun Hui Choi Sungil Jang Gye-Hyeong Woo Jeong-Heon Cha Eun-Jung Bak Yun-Jung Yoo |
| author_sort | Ji-Hye Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T09:39:47Z |
| format | Article |
| id | doaj.art-557a57e3a8854675b3fd89610256e812 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T09:39:47Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-557a57e3a8854675b3fd89610256e8122022-12-22T01:12:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011212e018970210.1371/journal.pone.0189702Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis.Ji-Hye KimAe Ri KimYun Hui ChoiSungil JangGye-Hyeong WooJeong-Heon ChaEun-Jung BakYun-Jung YooType 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.http://europepmc.org/articles/PMC5730195?pdf=render |
| spellingShingle | Ji-Hye Kim Ae Ri Kim Yun Hui Choi Sungil Jang Gye-Hyeong Woo Jeong-Heon Cha Eun-Jung Bak Yun-Jung Yoo Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis. PLoS ONE |
| title | Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis. |
| title_full | Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis. |
| title_fullStr | Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis. |
| title_full_unstemmed | Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis. |
| title_short | Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis. |
| title_sort | tumor necrosis factor α antagonist diminishes osteocytic rankl and sclerostin expression in diabetes rats with periodontitis |
| url | http://europepmc.org/articles/PMC5730195?pdf=render |
| work_keys_str_mv | AT jihyekim tumornecrosisfactoraantagonistdiminishesosteocyticranklandsclerostinexpressionindiabetesratswithperiodontitis AT aerikim tumornecrosisfactoraantagonistdiminishesosteocyticranklandsclerostinexpressionindiabetesratswithperiodontitis AT yunhuichoi tumornecrosisfactoraantagonistdiminishesosteocyticranklandsclerostinexpressionindiabetesratswithperiodontitis AT sungiljang tumornecrosisfactoraantagonistdiminishesosteocyticranklandsclerostinexpressionindiabetesratswithperiodontitis AT gyehyeongwoo tumornecrosisfactoraantagonistdiminishesosteocyticranklandsclerostinexpressionindiabetesratswithperiodontitis AT jeongheoncha tumornecrosisfactoraantagonistdiminishesosteocyticranklandsclerostinexpressionindiabetesratswithperiodontitis AT eunjungbak tumornecrosisfactoraantagonistdiminishesosteocyticranklandsclerostinexpressionindiabetesratswithperiodontitis AT yunjungyoo tumornecrosisfactoraantagonistdiminishesosteocyticranklandsclerostinexpressionindiabetesratswithperiodontitis |