Evidence map›Paper›PMID 30185903›Full record

ArticleNature2018

Coupling of bone resorption and formation by RANKL reverse signalling.

Yuki Ikebuchi, Shigeki Aoki, Masashi Honma, Madoka Hayashi, Yasutaka Sugamori, Masud Khan, Yoshiaki Kariya, Genki Kato, Yasuhiko Tabata, Josef M Penninger and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 308 papers.

0numbers the graph read from it
0cells of the map it votes in
308citing papers in PubMed
21.0field-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

308 citing papers in PubMed, 541 citations in OpenAlex.

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  10. Apoptotic bodies in bone homeostasis and skeletal disease: biology and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026
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248 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Yuki Ikebuchi *Department of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
Shigeki Aoki *Department of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
Masashi Honma *Department of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo, Tokyo, Japan. mhonma-tky@umin.ac.jp.
Madoka HayashiDepartment of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
Yasutaka SugamoriDepartment of Basic Oral Health Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Masud KhanDepartment of Basic Oral Health Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Yoshiaki KariyaDepartment of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
Genki KatoDepartment of Bio-Matrix (Pharmacology), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Yasuhiko TabataLaboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Josef M PenningerInstitute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria.
Nobuyuki UdagawaDepartment of Biochemistry, Matsumoto Dental University, Shiojiri, Japan.
Kazuhiro AokiDepartment of Basic Oral Health Engineering, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Hiroshi SuzukiDepartment of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
University of Tokyo Hospital · JPTokyo Medical and Dental University · JPAustrian Academy of Sciences · ATKyoto University · JPMatsumoto Dental University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Receptor activator of nuclear factor-kappa B (RANK) ligand (RANKL) binds RANK on the surface of osteoclast precursors to trigger osteoclastogenesis. Recent studies have indicated that osteocytic RANKL has an important role in osteoclastogenesis during bone remodelling; however, the role of osteoblastic RANKL remains unclear. Here we show that vesicular RANK, which is secreted from the maturing osteoclasts, binds osteoblastic RANKL and promotes bone formation by triggering RANKL reverse signalling, which activates Runt-related transcription factor 2 (Runx2). The proline-rich motif in the RANKL cytoplasmic tail is required for reverse signalling, and a RANKL(Pro29Ala) point mutation reduces activation of the reverse signalling pathway. The coupling of bone resorption and formation is disrupted in RANKL(Pro29Ala) mutant mice, indicating that osteoblastic RANKL functions as a coupling signal acceptor that recognizes vesicular RANK. RANKL reverse signalling is therefore a potential pharmacological target for avoiding the reduced bone formation associated with inhibition of osteoclastogenesis.

Indexed as

OsteogenesisSignal TransductionAmino Acid SubstitutionAnimalsBone ResorptionCell DifferentiationCore Binding Factor Alpha 1 SubunitCross-Linking ReagentsCytoplasmic VesiclesFemaleMaleMiceMice, Inbred C57BLOsteoblastsOsteoclastsRANK LigandCore Binding Factor Alpha 1 SubunitCross-Linking ReagentsRANK LigandReceptor Activator of Nuclear Factor-kappa BRunx2 protein, mouseTnfrsf11a protein, mouseTnfsf11 protein, mouse

Identifiers

PMID30185903
OpenAlexW2890611509

What OpenQuestion holds

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Read underepoch 390

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.