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Record W3191335158 · doi:10.1038/s41467-021-25124-2

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

2021· article· en· W3191335158 on OpenAlexafffund
Karin Nilsson, Petra Henning, Maha El Shahawy, Maria Nethander, Thomas Levin Andersen, Charlotte Ejersted, Jianyao Wu, Karin L. Gustafsson, Antti Koskela, Juha Tuukkanen, Pedro Paulo Chaves de Souza, Jan Tuckermann, Mattias Lorentzon, Linda Engström, Terho Lehtimäki, Jonathan H. Tobias, Sirui Zhou, Ulf H. Lerner, J. Brent Richards, Sofia Movérare‐Skrtic, Claes Ohlsson

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBone Metabolism and Diseases
Canadian institutionsMcGill UniversityJewish General Hospital
FundersAdlerbertska Research FoundationSahlgrenska AkademinMedical Research CouncilFonds de Recherche du Québec - SantéNational Institutes of HealthVetenskapsrådetKnut och Alice Wallenbergs StiftelseNovo NordiskPublic Health AgencyEuropean CommissionGöteborgs UniversitetJewish General HospitalKing's College LondonIngaBritt och Arne Lundbergs ForskningsstiftelseNational Institute for Health and Care ResearchAdlerbertska StiftelsernaNovo Nordisk FondenWellcome TrustCancer Research UKAcademy of FinlandCanadian Institutes of Health ResearchCompute CanadaPublic Health Agency of CanadaTays
KeywordsMedicine

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.763
Threshold uncertainty score0.337

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.283
Teacher spread0.275 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations39
Published2021
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicBone Metabolism and DiseasesFrench-language works237,207