Evidence map›Paper›PMID 42282586›Full record

ArticlebioRxiv : the preprint server for biology2026

Multiscale analysis and functional validation of the cellular and genetic determinants of skeletal disease.

Ryan C Chai, Mischa Lundberg, Bernard Freudenthal, James T Smith, Andrew P Boughton, Yuandan Zhang, Kaitlyn A Flynn, Monika Frysz, Alexander P Corr, Weng Hua Khoo and 41 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

51 authors.

Ryan C ChaiCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Mischa LundbergTransformational Bioinformatics, Commonwealth Scientific and Industrial Research Organisation, Sydney, NSW, Australia.
Bernard FreudenthalMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
James T SmithCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Andrew P BoughtonDepartment of Biostatistics and the Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Yuandan ZhangMater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia.
Kaitlyn A FlynnMater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia.
Monika FryszUniversity of Bristol, Musculoskeletal Research Unit, Bristol Medical School, Bristol, United Kingdom.
Alexander P CorrCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Weng Hua KhooCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Davide Komla-EbriMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Michael R G DackMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Siobhan E GuilfoyleMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
John G LoganMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Natalie C ButterfieldMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Victoria D LeitchMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Andrea S PollardMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Riikka E MäkitieMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Nathaniel BradfordSt. Vincent's Hospital, Darlinghurst, NSW, Australia.
Lorenzo Ramos-MucciRelation Therapeutics, London, UK.
Amaia Vilas-ZornozaRelation Therapeutics, London, UK.
Yunshun ChenWalter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Raymond K H YipWalter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Jeremy ErWalter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Siew Zhuan TanInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia.
Michelle M McDonaldSchool of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Scott E YoultenCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
C Marcelo SergioCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Ariel Castro-MartinezCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Shelley G YoungCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Elena SkorokhodovaCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
David M EvansUQ Frazer Institute, The University of Queensland, Woolloongabba, QLD, Australia.
Joseph E PowellTranslational Genomics Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Christiaan A de LeeuwDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, The Netherlands.
Adam D EwingMater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia.
John A EismanCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Robert D BlankCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Tri Giang PhanSchool of Clinical Medicine, Faculty of Medicine and Health, UNSW, Sydney, NSW, Australia.
International Federation of Musculoskeletal Research Societies (IFMRS) Big Data Working Group
Anne K LagendijkInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia.
Edwin D HawkinsWalter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Horng Lii OhSt. Vincent's Hospital, Darlinghurst, NSW, Australia.
Rebecca McIntyreRelation Therapeutics, London, UK.
Edith M HesselRelation Therapeutics, London, UK.
Jake P Taylor-KingRelation Therapeutics, London, UK.
Paul A BaldockCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Emma L DuncanSchool of Life Course & Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Graham R WilliamsMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
J H Duncan BassettMolecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Peter I CroucherCancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
John P KempMater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia.

Funding

RISK FACTORS FOR VERTEBRAL FRACTURE AND BONE LOSSR01AR041398 · NIAMS · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI KIEL, DOUGLAS P. · 1991 to 2025
$16.1M
NIAMS NIH HHS R01 AR041398Wellcome Trust
6 · The paper itself

Abstract

Musculoskeletal diseases are a major health burden. Development of bone-active therapies has been hindered by limited understanding of the cells and genes that regulate the skeleton. We exploited the value of cross-species analysis and developed single-cell methodologies in skeletal tissues to define the critical endosteal compartment that regulates bone turnover. Thirty-four distinct cell types were identified, and disease-relevant cells prioritised by enrichment for rare skeletal disorder genes and bone mineral density-associated genes in an extended UK Biobank GWAS. Functional validation was undertaken in over one thousand genetically modified mouse models. Endothelial and vascular smooth muscle cells were identified as novel skeletal disease-relevant cells alongside osteoblast, chondrocyte and osteoclast cell lineages. Hundreds of cell-specific genes with unappreciated roles in skeletal pathophysiology were identified. This comprehensive cellular and molecular framework underpins skeletal physiology and disease, and will help prioritise new therapeutic targets to accelerate development of novel therapies to treat musculoskeletal disease.

Identifiers

PMID42282586
PMCPMC13251937

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.