Evidence map›Paper›PMID 33079279›Full record

ReviewJournal of bone and mineral metabolism2021

Osteoclast differentiation by RANKL and OPG signaling pathways.

Nobuyuki Udagawa, Masanori Koide, Midori Nakamura, Yuko Nakamichi, Teruhito Yamashita, Shunsuke Uehara, Yasuhiro Kobayashi, Yuriko Furuya, Hisataka Yasuda, Chie Fukuda and 1 more

Abstract readReview
PubMed Publisher
In one paragraph

Review in Journal of bone and mineral metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 415 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
415citing papers in PubMed, 2 pooled it
23.7field-weighted citation impact, top 1% 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

415 citing papers in PubMed, 2 syntheses or guidelines pooled it, 633 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. S100A9 Induces RANKL Expression in Osteocytes Utilizing IL-6/sIL-6R Combination and gp130 Signaling Pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  17. Temporal immunomodulation of CD4Science advances · 2026
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355 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 1 country.

Nobuyuki UdagawaDepartment of Biochemistry, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano, 399-0781, Japan. nobuyuki.udagawa@mdu.ac.jp.
Masanori KoideDivision of Hard Tissue Research, I, nstitute for Oral Science, Matsumoto Dental University, Nagano, 399-0781, Japan.
Midori NakamuraDepartment of Biochemistry, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano, 399-0781, Japan.
Yuko NakamichiDivision of Hard Tissue Research, I, nstitute for Oral Science, Matsumoto Dental University, Nagano, 399-0781, Japan.
Teruhito YamashitaDivision of Hard Tissue Research, I, nstitute for Oral Science, Matsumoto Dental University, Nagano, 399-0781, Japan.
Shunsuke UeharaDepartment of Biochemistry, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano, 399-0781, Japan.
Yasuhiro KobayashiDivision of Hard Tissue Research, I, nstitute for Oral Science, Matsumoto Dental University, Nagano, 399-0781, Japan.
Yuriko FuruyaNagahama Institute for Biochemical Science, Oriental Yeast Co., Ltd., Nagahama, Japan.
Hisataka YasudaNagahama Institute for Biochemical Science, Oriental Yeast Co., Ltd., Nagahama, Japan.
Chie FukudaSpecialty Medicine Research Laboratories 1, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Eisuke TsudaSpecialty Medicine Research Laboratories 1, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Matsumoto Dental University · JPDaiichi-Sankyo (Japan) · JPNagahama Institute of Bio-Science and Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionIn bone tissue, bone resorption by osteoclasts and bone formation by osteoblasts are repeated continuously. Osteoclasts are multinucleated cells that derive from monocyte-/macrophage-lineage cells and resorb bone. In contrast, osteoblasts mediate osteoclastogenesis by expressing receptor activator of nuclear factor-kappa B ligand (RANKL), which is expressed as a membrane-associated cytokine. Osteoprotegerin (OPG) is a soluble RANKL decoy receptor that is predominantly produced by osteoblasts and which prevents osteoclast formation and osteoclastic bone resorption by inhibiting the RANKL-RANKL receptor interaction. MATERIALS AND

methodsIn this review, we would like to summarize our experimental results on signal transduction that regulates the expression of RANKL and OPG.

resultsUsing OPG gene-deficient mice, we have demonstrated that OPG and sclerostin produced by osteocytes play an important role in the maintenance of cortical and alveolar bone. In addition, it was shown that osteoclast-derived leukemia inhibitory factor (LIF) reduces the expression of sclerostin in osteocytes and promotes bone formation. WP9QY (W9) is a peptide that was designed to be structurally similar to one of the cysteine-rich TNF-receptortype-I domains. Addition of the W9 peptide to bone marrow culture simultaneously inhibited osteoclast differentiation and stimulated osteoblastic cell proliferation. An anti-sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) antibody inhibited multinucleated osteoclast formation induced by RANKL and macrophage colony-stimulating factor (M-CSF). Pit-forming activity of osteoclasts was also inhibited by the anti-Siglec-15 antibody. In addition, anti-Siglec-15 antibody treatment stimulated the appearance of osteoblasts in cultures of mouse bone marrow cells in the presence of RANKL and M-CSF.

conclusionsBone mass loss depends on the RANK-RANKL-OPG system, which is a major regulatory system of osteoclast differentiation induction, activation, and survival.

Indexed as

Cell DifferentiationSignal TransductionAnimalsHumansOsteoclastsOsteogenesisOsteoprotegerinRANK LigandOsteoprotegerinRANK LigandBone resorptionOPGOsteoblastOsteoclastRANKL

Identifiers

PMID33079279
OpenAlexW3093365748

What OpenQuestion holds

Textmetadata
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.