Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitis
Background: Diabetes-associated periodontitis (DPD) is an inflammatory and destructive disease of periodontal tissues in the diabetic population. The disease is manifested as more severe periodontal destruction and is more difficult to treat when compared with periodontitis (PD). Eldecalcitol (ELD)...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1070117/full |
| _version_ | 1811173065516646400 |
|---|---|
| author | Ruihan Gao Ruihan Gao Weidong Zhang Weidong Zhang Yujun Jiang Yujun Jiang Junzhe Zhai Jian Yu Hongrui Liu Hongrui Liu Minqi Li Minqi Li |
| author_facet | Ruihan Gao Ruihan Gao Weidong Zhang Weidong Zhang Yujun Jiang Yujun Jiang Junzhe Zhai Jian Yu Hongrui Liu Hongrui Liu Minqi Li Minqi Li |
| author_sort | Ruihan Gao |
| collection | DOAJ |
| description | Background: Diabetes-associated periodontitis (DPD) is an inflammatory and destructive disease of periodontal tissues in the diabetic population. The disease is manifested as more severe periodontal destruction and is more difficult to treat when compared with periodontitis (PD). Eldecalcitol (ELD) is a novel active vitamin D3 analog; however, little clinical evidence is available on its role on improving PD and DPD, and its specific mechanisms remain unclear. In this study, we evaluated the preventative effects of ELD toward PD and DPD and explored its underlying molecular mechanisms.Methods: Experimental PD and DPD mouse models were established by ligation combined with lipopolysaccharide (LPS) from Porphyromonas gingivalis injection in C57BL/6J and C57BLKS/J Iar- + Leprdb/+Leprdb (db/db) mice, respectively. Simultaneously, ELD (0.25 μg/kg) was orally administered to mice via an intragastric method. Micro-computed tomography (CT), hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and tartrate-resistant acid phosphatase (TRAP) staining were used to evaluate alveolar bone alterations in vivo. Flow cytometry, immunofluorescence, and real-time polymerase chain reaction (qRT-PCR) were also used to examine gene expression and probe systemic and local changes in Treg and Th17 cell numbers. Additionally, western blotting and immunofluorescence staining were used to examine changes in STAT3/STAT5 signaling.Results: Micro-CT and HE staining showed that the DPD group had higher alveolar bone loss when compared with the PD group. After applying ELD, alveolar bone loss decreased significantly in both PD and DPD groups, and particularly evident in the DPD group. IHC and TRAP staining also showed that ELD promoted osteoblast activity while inhibiting the number of osteoclasts, and after ELD treatment, the receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) ratio decreased. More importantly, this decreasing trend was more obvious in the DPD group. Flow cytometry and qRT-PCR also showed that the systemic Th17/Treg imbalance in PD and DPD groups was partially resolved when animals were supplemented with ELD, while immunofluorescence staining and qRT-PCR data showed the Th17/Treg imbalance was partially resolved in the alveolar bone of both ELD supplemented groups. Western blotting and immunofluorescence staining showed increased p-STAT5 and decreased p-STAT3 levels after ELD application.Conclusion: ELD exerted preventative effects toward PD and DPD by partially rectifying Th17/Treg cell imbalance via STAT3/STAT5 signaling. More importantly, given the severity of DPD, we found ELD was more advantageous in preventing DPD. |
| first_indexed | 2024-04-10T17:40:43Z |
| format | Article |
| id | doaj.art-14c8d7a768d8483192aa136f7ecf62b4 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-10T17:40:43Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-14c8d7a768d8483192aa136f7ecf62b42023-02-03T13:18:13ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-02-011110.3389/fbioe.2023.10701171070117Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitisRuihan Gao0Ruihan Gao1Weidong Zhang2Weidong Zhang3Yujun Jiang4Yujun Jiang5Junzhe Zhai6Jian Yu7Hongrui Liu8Hongrui Liu9Minqi Li10Minqi Li11Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, ChinaCenter of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, ChinaDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, ChinaCenter of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, ChinaDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, ChinaCenter of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, ChinaCenter of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, ChinaDepartment of Radiology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, ChinaDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, ChinaCenter of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, ChinaDepartment of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, ChinaCenter of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, ChinaBackground: Diabetes-associated periodontitis (DPD) is an inflammatory and destructive disease of periodontal tissues in the diabetic population. The disease is manifested as more severe periodontal destruction and is more difficult to treat when compared with periodontitis (PD). Eldecalcitol (ELD) is a novel active vitamin D3 analog; however, little clinical evidence is available on its role on improving PD and DPD, and its specific mechanisms remain unclear. In this study, we evaluated the preventative effects of ELD toward PD and DPD and explored its underlying molecular mechanisms.Methods: Experimental PD and DPD mouse models were established by ligation combined with lipopolysaccharide (LPS) from Porphyromonas gingivalis injection in C57BL/6J and C57BLKS/J Iar- + Leprdb/+Leprdb (db/db) mice, respectively. Simultaneously, ELD (0.25 μg/kg) was orally administered to mice via an intragastric method. Micro-computed tomography (CT), hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and tartrate-resistant acid phosphatase (TRAP) staining were used to evaluate alveolar bone alterations in vivo. Flow cytometry, immunofluorescence, and real-time polymerase chain reaction (qRT-PCR) were also used to examine gene expression and probe systemic and local changes in Treg and Th17 cell numbers. Additionally, western blotting and immunofluorescence staining were used to examine changes in STAT3/STAT5 signaling.Results: Micro-CT and HE staining showed that the DPD group had higher alveolar bone loss when compared with the PD group. After applying ELD, alveolar bone loss decreased significantly in both PD and DPD groups, and particularly evident in the DPD group. IHC and TRAP staining also showed that ELD promoted osteoblast activity while inhibiting the number of osteoclasts, and after ELD treatment, the receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) ratio decreased. More importantly, this decreasing trend was more obvious in the DPD group. Flow cytometry and qRT-PCR also showed that the systemic Th17/Treg imbalance in PD and DPD groups was partially resolved when animals were supplemented with ELD, while immunofluorescence staining and qRT-PCR data showed the Th17/Treg imbalance was partially resolved in the alveolar bone of both ELD supplemented groups. Western blotting and immunofluorescence staining showed increased p-STAT5 and decreased p-STAT3 levels after ELD application.Conclusion: ELD exerted preventative effects toward PD and DPD by partially rectifying Th17/Treg cell imbalance via STAT3/STAT5 signaling. More importantly, given the severity of DPD, we found ELD was more advantageous in preventing DPD.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1070117/fulldiabetes-associated periodontitisperiodontitisTh17/Treg balanceeldecalcitolSTAT3/STAT5 signaling |
| spellingShingle | Ruihan Gao Ruihan Gao Weidong Zhang Weidong Zhang Yujun Jiang Yujun Jiang Junzhe Zhai Jian Yu Hongrui Liu Hongrui Liu Minqi Li Minqi Li Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitis Frontiers in Bioengineering and Biotechnology diabetes-associated periodontitis periodontitis Th17/Treg balance eldecalcitol STAT3/STAT5 signaling |
| title | Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitis |
| title_full | Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitis |
| title_fullStr | Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitis |
| title_full_unstemmed | Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitis |
| title_short | Eldecalcitol effectively prevents alveolar bone loss by partially improving Th17/Treg cell balance in diabetes-associated periodontitis |
| title_sort | eldecalcitol effectively prevents alveolar bone loss by partially improving th17 treg cell balance in diabetes associated periodontitis |
| topic | diabetes-associated periodontitis periodontitis Th17/Treg balance eldecalcitol STAT3/STAT5 signaling |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1070117/full |
| work_keys_str_mv | AT ruihangao eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT ruihangao eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT weidongzhang eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT weidongzhang eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT yujunjiang eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT yujunjiang eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT junzhezhai eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT jianyu eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT hongruiliu eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT hongruiliu eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT minqili eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis AT minqili eldecalcitoleffectivelypreventsalveolarbonelossbypartiallyimprovingth17tregcellbalanceindiabetesassociatedperiodontitis |