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Record W3035432557 · doi:10.1101/2020.06.09.141812

<i>Dmp1Cre</i> -directed knockdown of PTHrP in murine decidua is associated with increased bone width and a life-long increase in strength specific to male progeny

2020· preprint· en· W3035432557 on OpenAlexaff
Niloufar Ansari, Tsuyoshi Isojima, Blessing Crimeen‐Irwin, Ingrid J. Poulton, Narelle E. McGregor, P.W.M. Ho, Christopher S. Kovács, Evdokia Dimitriadis, Jonathan H. Gooi, T. John Martin, Natalie A. Sims

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldMedicine
TopicGrowth Hormone and Insulin-like Growth Factors
Canadian institutionsMemorial University of Newfoundland
FundersNational Health and Medical Research CouncilMedical Research CouncilState Government of VictoriaUniversity of Melbourne
KeywordsGene knockdownEndocrinologyDeciduaInternal medicineOsteopeniaEmbryonic stem cellWeaningBiologyAndrologyGeneBone mineralMedicineFetusPregnancyGeneticsOsteoporosisPlacenta

Abstract

fetched live from OpenAlex

Abstract Parathyroid hormone related-protein (PTHrP) is a pleiotropic regulator of tissue homeostasis. In bone, knockdown in osteocytes by Dmp1Cre- targeted deletion causes osteopenia and impaired strength. We report that this outcome depends on parental genotype. Adult Dmp1Cre.Pthlh f/f mice from homozygous parents ( Dmp1Cre.Pthlh f/f(hom) ) have stronger bones, with 40% more trabecular bone mass and 30% greater femoral width than controls. At 12 days old, greater bone width was also found in male and female Dmp1Cre.Pthlh f/f(hom) mice, but not in gene-matched mice from heterozygous parents, suggesting a maternal influence before weaning. Milk PTHrP levels were normal, but decidua from mothers of Dmp1Cre.Pthlh f/f(hom) mice were smaller, with low PTHrP levels. Moreover, Dmp1Cre.Pthlh f/f(hom) embryonic bone was more mineralized and wider than control. We conclude that Dmp1Cre leads to gene recombination in decidua, and that decidual PTHrP influences decidual cell maturation and limits embryonic bone growth. This identifies a maternal-derived developmental origin of adult bone strength.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.014
GPT teacher head0.211
Teacher spread0.197 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations1
Published2020
Admission routes1
Has abstractyes

Explore more

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