Evidence map›Paper›PMID 34984683›Full record

ArticleJournal of periodontal research2022

A novel adiponectin receptor agonist (AdipoAI) ameliorates type 2 diabetes-associated periodontitis by enhancing autophagy in osteoclasts.

Xingwen Wu, Yang Sun, Renjie Cui, Wei Qiu, Jin Zhang, Zhekai Hu, Wei Bi, Fei Yang, Duan Ma, Thomas Van Dyke and 3 more

Open access · greenAbstract read
In one paragraph

Article in Journal of periodontal research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
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  3. Review
  4. Article
  5. Review
  6. Review
  7. Antidiabetic features of AdipoAI, a novel AdipoR agonist.Cell biochemistry and function · 2024
    Article
  8. Article
  9. Review
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 3 countries.

Xingwen WuDepartment of Dentistry, Zhongshan Hospital, Fudan University, Shanghai, China.
Yang SunDepartment of Dentistry, Zhongshan Hospital, Fudan University, Shanghai, China.
Renjie CuiKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Wei QiuDivision of Oral Biology, Tufts University School of Dental Medicine, Boston, USA.
Jin ZhangKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Zhekai HuDivision of Oral Biology, Tufts University School of Dental Medicine, Boston, USA.
Wei BiDepartment of Dentistry, Zhongshan Hospital, Fudan University, Shanghai, China.
Fei YangDepartment of Dentistry, Zhongshan Hospital, Fudan University, Shanghai, China.
Duan MaKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Thomas Van DykeClinical and Translational Research, Forsyth Institute, Cambridge,, Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, USA.
Qisheng TuDivision of Oral Biology, Tufts University School of Dental Medicine, Boston, USA.ORCID https://orcid.org/0000-0003-0639-8761
Youcheng YuDepartment of Dentistry, Zhongshan Hospital, Fudan University, Shanghai, China.
Jake ChenDepartment of Dentistry, Zhongshan Hospital, Fudan University, Shanghai, China.
Tufts University · USSun Yat-sen University · CNFudan University · CNBoston University · US

Funding

Mechanisms of Resolvin E1 in Periodontal RegenerationR01DE025020 · NIDCR · ADA FORSYTH INSTITUTE, INC. · PI GUASTALDI, FERNANDO, VAN DYKE, THOMAS ELLIOTT · 2015 to 2023
$4.9M
Roles of Noncoding RNA in Bone RegenerationR01DE025681 · NIDCR · TUFTS UNIVERSITY BOSTON · PI CHEN, JAKE JINKUN · 2016 to 2024
$4.5M
A Long Noncoding RNA Amerliorates Periodontitis via Distinct Epigenetic PathwaysR01DE030074 · NIDCR · TUFTS UNIVERSITY BOSTON · PI CHEN, JAKE JINKUN · 2021 to 2025
$3.5M
Potentials of Epigenetic Molecules in Attenuating the Phenotypes of PeriodontitisR01DE032006 · NIDCR · TUFTS UNIVERSITY BOSTON · PI JAKE JINKUN CHEN · 2023 to 2026
$2.0M
Alveolar Bone Regeneration in Diabetic PeriodontitisR01DE026507 · NIDCR · TUFTS UNIVERSITY BOSTON · PI CHEN, JAKE JINKUN · 2017 to 2021
$2.0M
National Natural Science Foundation of China #81670956National Natural Science Foundation of China #81870793NIDCR NIH HHS R01 DE025020NIDCR NIH HHS R01 DE025681NIDCR NIH HHS R01 DE026507NIDCR NIH HHS R01 DE030074NIDCR NIH HHS R01 DE032006NIH HHS R01DE25681NIH HHS R01DE26507NIH HHS R01DE30074Shanghai Committee of Science and Technology to Youcheng Yu; and Zhongshan Hospital Young Scholar Project #2020ZSQN18Shanghai Cooperative International Project #16520710400Shanghai Sailing Program #21YF1406600Thomas Van Dyke R01DE25020
6 · The paper itself

Abstract

BACKGROUND AND

objectiveType 2 diabetes (T2D)-associated periodontitis is severe and refractory in many cases. Considered an inflammatory disease, T2D predisposes to periodontitis by increasing whole-body inflammation. One mechanism of increased inflammation is thatT2D is mediated by loss of production or function of the anti-inflammatory hormone adiponectin. In our previous report, AdipoRon, an adiponectin receptor agonist, and AdipoAI, a newly discovered, more specific agonist, attenuated T2D-associated inflammation by inhibiting osteoclastogenesis and LPS-induced endotoxemia. Autophagy plays an important role during osteoclast differentiation and function. The impact of AdipoAI on osteoclast function and autophagy involved in osteoclastogenesis is not known. Here, we compare AdipoRon and AdipoAI potency, side effects and mechanism of action in T2D-associated periodontitis.

methodsThe RAW 264.7 cell line was used for in vitro studies. We analyzed the potential cytotoxicity of AdipoAI using the CCK-8 assay. The anti-osteoclastogenic potential of AdipoAI was studied by real-time qPCR and tartrate-resistant acid phosphatase staining. The actions of AdipoAI involved in autophagy were tested by real-time qPCR, western blot and immunofluorescence staining. In the diet-induced obesity model of T2D, we investigated the impact of AdipoAI on fasting blood glucose, alveolar bone loss, and gingival inflammation in mice with experimental periodontitis.

resultsAdipoRon inhibited osteoclastogenesis and AdipoAI inhibited osteoclastogenesis at lower doses than AdipoRon without any cytotoxicity. In DIO mice with experimental periodontitis, AdipoAI reduced mouse body weight in 14 days, reducing fasting glucose levels, alveolar bone destruction, osteoclast number along the alveolar bone surface, and decreased the expression of pro-inflammatory factors in periodontal tissues. AdipoAI and AdipoRon also enhanced LC3A/B expression when cultured with RANKL.3-Methyladenine, a known autophagy inhibitor, decreased LC3A/B expression and reversed the inhibition of osteoclastogenesis during AdipoAI treatment.

conclusionsOur results demonstrate that AdipoAI ameliorates the severity of T2D-associated periodontitis by enhancing autophagy in osteoclasts at lower doses than AdipoRon without demonstrable side effects. Thus, AdipoAI has pharmaceutical potential for treating diabetes-associated periodontal disease.

Indexed as

Alveolar Bone LossDiabetes Mellitus, Type 2PeriodontitisAdiponectinAnimalsAutophagyMiceOsteoclastsRANK LigandReceptors, AdiponectinAdiponectinRANK LigandReceptors, AdiponectinAdiponectin receptor agonistautophagyDiet-Induced ObesityPeriodontitisType 2 Diabetes

Identifiers

PMID34984683
PMCPMC9380722
OpenAlexW4205207216

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.