Evidence mapPaperPMID 34389713Full record

ArticleNature communications2021

RSPO3 is important for trabecular bone and fracture risk in mice and humans.

Karin H Nilsson, Petra Henning, Maha El Shahawy, Maria Nethander, Thomas Levin Andersen, Charlotte Ejersted, Jianyao Wu, Karin L Gustafsson, Antti Koskela, Juha Tuukkanen and 11 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

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  15. Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023
    Review
  16. Review
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  18. High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023
    Review
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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

21 authors at 10 institutions in 9 countries.

Karin H Nilsson *Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Petra Henning *Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Maha El ShahawySahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0001-7122-1191
Maria NethanderSahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-3688-906X
Thomas Levin AndersenDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark.ORCID http://orcid.org/0000-0002-6981-7276
Charlotte EjerstedDepartment of Endocrinology, Odense University Hospital, Odense, Denmark.
Jianyao WuSahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Karin L GustafssonSahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0003-2082-4886
Antti KoskelaDepartment of Anatomy and Cell Biology, Faculty of Medicine, Institute of Cancer Research and Translational Medicine, University of Oulu, Oulu, Finland.
Juha TuukkanenDepartment of Anatomy and Cell Biology, Faculty of Medicine, Institute of Cancer Research and Translational Medicine, University of Oulu, Oulu, Finland.ORCID http://orcid.org/0000-0002-1723-6461
Pedro P C SouzaInnovation in Biomaterials Laboratory, Faculty of Dentistry, Federal University of Goiás, Goiâna, Brazil.ORCID http://orcid.org/0000-0001-7266-6061
Jan TuckermannInstitute of Comparative Molecular Endocrinology (CME), University of Ulm, Ulm, Germany.ORCID http://orcid.org/0000-0003-3691-275X
Mattias LorentzonSahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Linda Engström RuudDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.ORCID http://orcid.org/0000-0002-2555-4427
Jon H TobiasMusculoskeletal Research Unit, Translational Health Sciences, and Medical Research Council Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
Sirui ZhouDepartment of Medicine, Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0003-4963-0815
Ulf H Lerner *Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
J Brent Richards *Department of Medicine, Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada.ORCID http://orcid.org/0000-0002-3746-9086
Sofia Movérare-Skrtic *Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. sofia.skrtic@gu.se.ORCID http://orcid.org/0000-0001-7982-7438
Claes Ohlsson *Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. claes.ohlsson@medic.gu.se.ORCID http://orcid.org/0000-0002-9633-2805
University of Gothenburg · SESahlgrenska University Hospital · SEJewish General Hospital · CAUniversity of Oulu · FIOdense University Hospital · DKTampere University of Applied Sciences · FIUniversidade Federal de Goiás · BRUniversität Ulm · DEUniversity of Bristol · GBUniversity of Southern Denmark · DK

Funding

Cancer Research UKCIHR 365825CIHR 409511Department of HealthMedical Research CouncilWellcome Trust
6 · The paper itself

Abstract

With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.

Indexed as

Polymorphism, Single NucleotideAnimalsBone DensityCancellous BoneCell DifferentiationCell ProliferationCells, CulturedFractures, BoneGenetic Predisposition to DiseaseHumansMendelian Randomization AnalysisMiceMice, KnockoutMice, TransgenicOsteoblastsRisk FactorsRSPO3 protein, humanR-spondin3 protein, mouseR-SpondinsThrombospondins

Identifiers

PMID34389713
PMCPMC8363747
OpenAlexW3191335158

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.