Evidence map›Paper›PMID 27343691›Full record

ArticleFree radical biology & medicine2016

TRAP-positive osteoclast precursors mediate ROS/NO-dependent bactericidal activity via TLR4.

Kazuaki Nishimura, Satoru Shindo, Alexandru Movila, Rayyan Kayal, Albassam Abdullah, Irma Josefina Savitri, Atsushi Ikeda, Tsuguno Yamaguchi, Mohammed Howait, Ayman Al-Dharrab and 3 more

Open access · greenAbstract read
In one paragraph

Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 33 citations in OpenAlex.

  1. International journal of molecular sciences · 2026
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  3. RANKeLife · 2023
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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

13 authors at 6 institutions in 4 countries.

Kazuaki NishimuraThe Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, USA; Tohoku University Hospital, Maxillo-oral Disorders, Sendai, Japan. Electronic address: knishimura@dent.tohoku.ac.jp.
Satoru ShindoThe Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, USA; The University of Tokushima Graduate School, Department of Conservative Dentistry, Institute of Health Biosciences, Tokushima, Japan. Electronic address: c301351004@tokushima-u.ac.jp.
Alexandru MovilaThe Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, USA. Electronic address: amovila@forsyth.org.
Rayyan KayalKing Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia. Electronic address: rkayal@kau.edu.sa.
Albassam AbdullahThe Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, USA; King Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia. Electronic address: albassam.a@hotmail.com.
Irma Josefina SavitriAirlangga University, Department of Periodontics, Jawa Timur, Indonesia. Electronic address: irmaudijanto@gmail.com.
Atsushi IkedaThe Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, USA. Electronic address: aikeda@forsyth.org.
Tsuguno YamaguchiThe Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, USA; Research and Development Headquarters, LION Corporation, 100 Tajima Odawara, Kanagawa, Japan. Electronic address: tsuguno@gmail.com.
Mohammed HowaitKing Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia. Electronic address: mhowait@icloud.com.
Ayman Al-DharrabKing Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia. Electronic address: aaldharab@kau.edu.sa.
Abdulghani MiraKing Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia. Electronic address: amira@kau.edu.sa.
Xiaozhe HanThe Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, USA; Harvard School of Dental Medicine, Department of Oral Medicine, Infection and Immunity, Boston, MA, USA. Electronic address: XHan@forsyth.org.
Toshihisa KawaiThe Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, USA; Harvard School of Dental Medicine, Department of Oral Medicine, Infection and Immunity, Boston, MA, USA. Electronic address: tkawai@forsyth.org.
King Abdulaziz University · SAHarvard University · USAirlangga University · IDLion Corporation (Japan) · JPTohoku University Hospital · JPTokushima University · JP

Funding

Regulatory B Cells in the Amelioration of Immune-Mediated Periodontal DiseaseR01DE025255 · NIDCR · NOVA SOUTHEASTERN UNIVERSITY · PI HAN, XIAOZHE · 2015 to 2025
$5.8M
FORSYTH POSTDOCTORAL TRAINING IN ORAL HEALTH RESEARCHT32DE007327 · NIDCR · FORSYTH INSTITUTE · PI VAN DYKE, THOMAS ELLIOTT · 2001 to 2015
$3.5M
Programming dendritic cells in concert with morphagen delivery for periodontal reR01DE019917 · NIDCR · HARVARD UNIVERSITY · PI KAWAI, TOSHIHISA, MOONEY, DAVID J · 2009 to 2013
$3.5M
T-Regulatory Cells in PeriodontitisR01DE018499 · NIDCR · ADA FORSYTH INSTITUTE, INC. · PI KAWAI, TOSHIHISA · 2008 to 2011
$1.9M
Regulation of B-Cell Apoptosis by TLR Signaling in Periodontal DiseaseR21DE021837 · NIDCR · ADA FORSYTH INSTITUTE, INC. · PI HAN, XIAOZHE · 2011 to 2012
$543k
Regulatory B cells in the amelioration of immune-mediated periodontal diseaseR56DE023807 · NIDCR · ADA FORSYTH INSTITUTE, INC. · PI HAN, XIAOZHE · 2014 to 2014
$476k
NIDCR NIH HHS L30 DE020037NIDCR NIH HHS R01 DE018499NIDCR NIH HHS R01 DE019917NIDCR NIH HHS R01 DE025255NIDCR NIH HHS R21 DE021837NIDCR NIH HHS R56 DE023807NIDCR NIH HHS T32 DE007327
6 · The paper itself

Abstract

Osteoclastogenesis was induced by RANKL stimulation in mouse monocytes to examine the possible bactericidal function of osteoclast precursors (OCp) and mature osteoclasts (OCm) relative to their production of NO and ROS. Tartrate-resistant acid phosphatase (TRAP)-positive OCp, but few or no OCm, phagocytized and killed Escherichia coli in association with the production of reactive oxygen species (ROS) and nitric oxide (NO). Phagocytosis of E. coli and production of ROS and NO were significantly lower in TRAP+ OCp derived from Toll-like receptor (TLR)-4 KO mice than that derived from wild-type (WT) or TLR2-KO mice. Interestingly, after phagocytosis, TRAP+ OCp derived from wild-type and TLR2-KO mice did not differentiate into OCm, even with continuous exposure to RANKL. In contrast, E. coli-phagocytized TRAP+ OCp from TLR4-KO mice could differentiate into OCm. Importantly, neither NO nor ROS produced by TRAP+ OCp appeared to be engaged in phagocytosis-induced suppression of osteoclastogenesis. These results suggested that TLR4 signaling not only induces ROS and NO production to kill phagocytized bacteria, but also interrupts OCm differentiation. Thus, it can be concluded that TRAP+ OCp, but not OCm, can mediate bactericidal activity via phagocytosis accompanied by the production of ROS and NO via TLR4-associated reprograming toward phagocytic cell type.

Indexed as

AnimalsEscherichia coliMiceMice, Inbred C57BLMice, KnockoutMicrobial ViabilityNitric OxideOsteoclastsPhagocytosisRANK LigandRAW 264.7 CellsReactive Oxygen SpeciesTartrate-Resistant Acid PhosphataseToll-Like Receptor 4Acp5 protein, mouseNitric OxideRANK LigandReactive Oxygen SpeciesTartrate-Resistant Acid PhosphataseTlr4 protein, mouseTnfsf11 protein, mouseToll-Like Receptor 4BacteriaNitric oxideOsteoclastPhagocytosisRANKLReactive oxygen speciesTartrate-resistant acid phosphataseToll-like receptor

Identifiers

PMID27343691
PMCPMC5654318
OpenAlexW2466555003

What OpenQuestion holds

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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.