Evidence map›Paper›PMID 25952706›Full record

ArticleJournal of clinical periodontology2015

Ac45 silencing mediated by AAV-sh-Ac45-RNAi prevents both bone loss and inflammation caused by periodontitis.

Zheng Zhu, Wei Chen, Liang Hao, Guochun Zhu, Yun Lu, Sheng Li, Lin Wang, Yi-Ping Li

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical periodontology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

7 citing papers in PubMed, 16 citations in OpenAlex.

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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

8 authors at 4 institutions in 3 countries.

Zheng ZhuJiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
Wei ChenDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Liang HaoDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Guochun ZhuDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Yun LuDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Sheng LiJiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
Lin WangJiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
Yi-Ping LiDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
University of Alabama at Birmingham · USNanjing Library · CNNanjing Medical University · CNWan Fang Hospital · TW

Funding

UAB Core Center for Musculoskeletal DisordersP30AR046031 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PONNAZHAGAN, SELVARANGAN · 2001 to 2010
$5.6M
TRANSCRIPTION FACTORS CONTROL OSTEOCLAST DIFFERENTIATIONR01AR044741 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LI, YI-PING · 1999 to 2016
$5.1M
Inhibiting Periodontitis by Targeting Cathepsin K and Attenuating TLR SignalingR01DE023813 · NIDCR · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LI, YI-PING · 2014 to 2023
$3.9M
NIAMS NIH HHS P30 AR046031NIAMS NIH HHS P30AR046031NIAMS NIH HHS R01 AR044741NIDCR NIH HHS R01 DE023813NINDS NIH HHS P30NS0474666
6 · The paper itself

Abstract

aimPeriodontitis induced by oral pathogens leads to severe periodontal tissue damage and osteoclast-mediated bone resorption caused by inflammation. On the basis of the importance of Ac45 in osteoclast formation and function, we performed this study to evaluate the therapeutic potential of periodontitis by local adeno-associated virus (AAV)-mediated Ac45 gene knockdown. MATERIAL AND

methodsWe used AAV-mediated short hairpin RNAi knockdown of Ac45 gene expression (AAV-sh-Ac45) to inhibit bone erosion and gingival inflammation simultaneously in a well-established periodontitis mouse model induced by Porphyromonas gingivalis W50. Histological studies were performed to evaluate the bone protection of AAV-sh-Ac45. Immunochemistry, ELISA and qRT-PCR were performed to reveal the role of Ac45 knockdown on inflammation, immune response and expression of cytokine.

resultsWe found that Ac45 knockdown impaired osteoclast-mediated extracellular acidification and bone resorption in vitro and in vivo. Furthermore, local administration of AAV-sh-Ac45 protected mice from bone erosion by >85% and attenuated inflammation and decreased infiltration of T cells, dendritic cells and macrophages in the periodontal lesion. Notably, the expression of pro-inflammatory cytokines was also reduced.

conclusionsLocal AAV-sh-Ac45 gene therapy efficiently protects against periodontal tissue damage and bone erosion through both inhibition of osteoclast function and attenuating inflammation, and may represent a powerful new treatment strategy for periodontitis.

Indexed as

Gene SilencingRNA InterferenceAlveolar Bone LossAnimalsBacteroidaceae InfectionsCytokinesDendritic CellsDependovirusDisease Models, AnimalFemaleGene Knockdown TechniquesGingivitisInflammation MediatorsMacrophagesMiceMice, Inbred BALB CAtp6ap1 protein, mouseCytokinesInflammation MediatorsRNA, Small InterferingVacuolar Proton-Translocating ATPasesAAV-mediated RNAi knockdownAc45alveolar bone resorptiongene therapygingival inflammationosteoclast immunologyperiodontal disease

Identifiers

PMID25952706
PMCPMC4620917
OpenAlexW1923395112

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.