Evidence map›Paper›PMID 33793647›Full record

ArticlePloS one2021

Human osteoclastogenesis in Epstein-Barr virus-induced erosive arthritis in humanized NOD/Shi-scid/IL-2Rγnull mice.

Yosuke Nagasawa, Masami Takei, Mitsuhiro Iwata, Yasuko Nagatsuka, Hiroshi Tsuzuki, Kenichi Imai, Ken-Ichi Imadome, Shigeyoshi Fujiwara, Noboru Kitamura

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 39% 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

5 citing papers in PubMed, 9 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

9 authors at 2 institutions in 1 country.

Yosuke NagasawaDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.ORCID 0000-0003-3416-1649
Masami TakeiDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Mitsuhiro IwataDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Yasuko NagatsukaDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hiroshi TsuzukiDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Kenichi ImaiDepartment of Microbiology, Nihon University School of Dentistry, Tokyo, Japan.
Ken-Ichi ImadomeDepartment of Advanced Medicine for Infections, National Center for Child Health and Development, Tokyo, Japan.
Shigeyoshi FujiwaraDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.ORCID 0000-0002-5823-5991
Noboru KitamuraDivision of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Nihon University · JPNational Center For Child Health and Development · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many human viruses, including Epstein-Barr virus (EBV), do not infect mice, which is challenging for biomedical research. We have previously reported that EBV infection induces erosive arthritis, which histologically resembles rheumatoid arthritis, in humanized NOD/Shi-scid/IL-2Rγnull (hu-NOG) mice; however, the underlying mechanisms are not known. Osteoclast-like multinucleated cells were observed during bone erosion in this mouse model, and therefore, we aimed to determine whether the human or mouse immune system activated bone erosion and analyzed the characteristics and origin of the multinucleated cells in hu-NOG mice. Sections of the mice knee joint tissues were immunostained with anti-human antibodies against certain osteoclast markers, including cathepsin K and matrix metalloproteinase-9 (MMP-9). Multinucleated cells observed during bone erosion stained positively for human cathepsin K and MMP-9. These results indicate that human osteoclasts primarily induce erosive arthritis during EBV infections. Human osteoclast development from hematopoietic stem cells transplanted in hu-NOG mice remains unclear. To confirm their differentiation potential into human osteoclasts, we cultured bone marrow cells of EBV-infected hu-NOG mice and analyzed their characteristics. Multinucleated cells cultured from the bone marrow cells stained positive for human cathepsin K and human MMP-9, indicating that bone marrow cells of hu-NOG mice could differentiate from human osteoclast progenitor cells into human osteoclasts. These results indicate that the human immune response to EBV infection may induce human osteoclast activation and cause erosive arthritis in this mouse model. Moreover, this study is the first, to our knowledge, to demonstrate human osteoclastogenesis in humanized mice. We consider that this model is useful for studying associations of EBV infections with rheumatoid arthritis and human bone metabolism.

Indexed as

Cell DifferentiationOsteogenesisAnimalsArthritisBone Marrow CellsCathepsin KDisease Models, AnimalHerpesvirus 4, HumanHumansInterleukin Receptor Common gamma SubunitKnee JointMatrix Metalloproteinase 9MiceMice, Inbred NODMice, SCIDMice, TransgenicCathepsin KInterleukin Receptor Common gamma SubunitMatrix Metalloproteinase 9

Identifiers

PMID33793647
PMCPMC8029598
OpenAlexW3146008850

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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.