Evidence map›Paper›PMID 25306233›Full record

ArticleNature medicine2014

Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures.

Sofia Movérare-Skrtic, Petra Henning, Xianwen Liu, Kenichi Nagano, Hiroaki Saito, Anna E Börjesson, Klara Sjögren, Sara H Windahl, Helen Farman, Bert Kindlund and 21 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
221citing papers in PubMed, 2 pooled it
11.8field-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

221 citing papers in PubMed, 2 syntheses or guidelines pooled it, 369 citations in OpenAlex.

  1. A Meta-Analysis of the Transferability of Bone Mineral Density Genetic Loci Associations From European to African Ancestry Populations.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021
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161 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

31 authors at 11 institutions in 5 countries.

Sofia Movérare-SkrticCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Petra HenningCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Xianwen Liu1] Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA. [2] State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Sichuan, China.
Kenichi NaganoDepartment of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
Hiroaki SaitoDepartment of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
Anna E BörjessonCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Klara SjögrenCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Sara H WindahlCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Helen FarmanCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Bert KindlundCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Cecilia EngdahlCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Antti KoskelaDepartment of Anatomy and Cell Biology, Medical Research Center, University of Oulu, Oulu, Finland.
Fu-Ping ZhangTurku Center for Disease Modeling, Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
Emma E ErikssonDepartment of Women's and Children's Health, Karolinska Institutet, Pediatric Endocrinology Unit, Stockholm, Sweden.
Farasat Zaman1] Department of Women's and Children's Health, Karolinska Institutet, Pediatric Endocrinology Unit, Stockholm, Sweden. [2] Developmental and Stem Cell Biology, the Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Ann HammarstedtLundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Hanna Isaksson1] Department of Biomedical Engineering, Lund University, Lund, Sweden. [2] Department of Orthopedics, Lund University, Lund, Sweden.
Marta BallyDepartment of Applied Physics, Division of Biological Physics, Chalmers University of Technology, Gothenburg, Sweden.
Ali KassemMolecular Periodontology, Umeå University, Umeå, Sweden.ORCID 0000000218208518
Catharina LindholmCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Olof SandbergOrthopaedics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Per AspenbergOrthopaedics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Lars SävendahlDepartment of Women's and Children's Health, Karolinska Institutet, Pediatric Endocrinology Unit, Stockholm, Sweden.
Jian Q FengDepartment of Biomedical Sciences, Baylor College of Dentistry, Texas A&M Health Science Center, Dallas, Texas, USA.
Jan TuckermannInstitute of General Zoology and Endocrinology, University of Ulm, Ulm, Germany.
Juha TuukkanenDepartment of Anatomy and Cell Biology, Medical Research Center, University of Oulu, Oulu, Finland.
Matti Poutanen1] Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. [2] Turku Center for Disease Modeling, Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
Roland Baron1] Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA. [2] Department of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ulf H Lerner1] Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. [2] Molecular Periodontology, Umeå University, Umeå, Sweden.
Francesca Gori1] Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA. [2] Department of Medicine, Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Claes OhlssonCentre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
University of Gothenburg · SEHarvard University · USKarolinska Institutet · SELinköping University · SEUniversity of Oulu · FIUniversity of Turku · FIChalmers University of Technology · SELund University · SETexas A&M Health Science Center · USUmeå University · SEUniversität Ulm · DE

Funding

R-Spondin3 as a target for anabolic bone therapyR01AR064724 · NIAMS · HARVARD MEDICAL SCHOOL · PI BARON, ROLAND E · 2014 to 2018
$2.7M
NIAMS NIH HHS R01 AR064724NIAMS NIH HHS R01AR064724
6 · The paper itself

Abstract

The WNT16 locus is a major determinant of cortical bone thickness and nonvertebral fracture risk in humans. The disability, mortality and costs caused by osteoporosis-induced nonvertebral fractures are enormous. We demonstrate here that Wnt16-deficient mice develop spontaneous fractures as a result of low cortical thickness and high cortical porosity. In contrast, trabecular bone volume is not altered in these mice. Mechanistic studies revealed that WNT16 is osteoblast derived and inhibits human and mouse osteoclastogenesis both directly by acting on osteoclast progenitors and indirectly by increasing expression of osteoprotegerin (Opg) in osteoblasts. The signaling pathway activated by WNT16 in osteoclast progenitors is noncanonical, whereas the pathway activated in osteoblasts is both canonical and noncanonical. Conditional Wnt16 inactivation revealed that osteoblast-lineage cells are the principal source of WNT16, and its targeted deletion in osteoblasts increases fracture susceptibility. Thus, osteoblast-derived WNT16 is a previously unreported key regulator of osteoclastogenesis and fracture susceptibility. These findings open new avenues for the specific prevention or treatment of nonvertebral fractures, a substantial unmet medical need.

Indexed as

OsteogenesisAgingAnimalsCell DifferentiationCell LineCell LineageCells, CulturedDisease SusceptibilityFractures, BoneGene DeletionGene Expression RegulationHumansMice, Inbred C57BLOrgan SizeOsteoblastsOsteoclastsOsteoprotegerinRANK LigandRNA, MessengerWNT16 protein, humanWnt16 protein, mouseWnt Proteins

Identifiers

PMID25306233
PMCPMC4392888
OpenAlexW2037978897

What OpenQuestion holds

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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.