Evidence map›Paper›PMID 42297796›Full record

ArticleBone research2026

Murine model of high bone mass osteogenesis imperfecta exhibits bone matrix hyper-mineralization, misaligned mineral crystals, and altered osteoblast differentiation.

Aileen M Barnes, M Helen Rajpar, Joseph E Perosky, Stéphane Blouin, Basma Khoury, MaryAnn Weis, Theresa Hefferan, Alberta Derkyi, Gali Guterman-Ram, Ghazal Hedjazi and 8 more

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Article in Bone research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

18 authors.

Aileen M BarnesSection on Heritable Disorders of Bone and Extracellular Matrix, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-8021-4997
M Helen RajparSection on Heritable Disorders of Bone and Extracellular Matrix, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Joseph E PeroskyDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Stéphane BlouinLudwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Department Hanusch Hospital, Vienna, Austria.ORCID 0000-0001-6575-8443
Basma KhouryDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
MaryAnn WeisDepartment of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA, USA.
Theresa HefferanBiomaterials and Histomorphometry Core Laboratory, Mayo Clinic, Rochester, MN, USA.
Alberta DerkyiOffice of the Clinical Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Gali Guterman-RamSection on Heritable Disorders of Bone and Extracellular Matrix, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Ghazal HedjaziLudwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Department Hanusch Hospital, Vienna, Austria.
Kiersten CampbellBioinformatics & Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
Chris StephanDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
David R EyreVienna Bone and Growth Center, Vienna, Austria.
Ryan K DaleBioinformatics & Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
Peter FratzlMax Planck Institute of Colloids and Interfaces, Potsdam, Germany.
Kenneth M KozloffDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Nadja Fratzl-ZelmanLudwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Med. Department Hanusch Hospital, Vienna, Austria.
Joan C MariniSection on Heritable Disorders of Bone and Extracellular Matrix, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. oidoc@helix.nih.gov.

Funding

NIH Intramural Research Program of the National Institutes of Health
6 · The paper itself

Abstract

Osteogenesis imperfecta (OI), characterized by bone fragility and low bone mass, is predominantly caused by mutations in type I collagen. High bone mass OI (HBM OI) is a rare form caused by heterozygous missense mutations at the type I procollagen C-propeptide cleavage site. Knock-in HBM OI mice were generated to elucidate the effect of this mutation on cells and bone. HBM OI murine femora contain increased monomeric pro-α1(I)C-propeptide and pC-collagen; their bone collagen fibrils have a "barbed-wire" appearance. Decreased C-propeptide cleavage diminishes bone strength. HBM OI femora are extremely brittle, with thin cortices, decreased BV/TV, and fracture load. The cortical bone has increased mineral content, with thinner, more disorganized mineral particles. Increased expression of ossification genes in both murine and human HBM OI osteoblasts during in vitro differentiation and increased mineral deposition in culture indicate impaired C-propeptide processing affects cellular processes related to mineralization, rather than being a passive matrix process. Gene ontology analysis of RNA-seq data from differentiating HBM OI osteoblasts revealed top upregulated pathways for ossification, mineralization, and osteoblast differentiation (5-25×) while top-downregulated pathways involved cellular adhesion, migration, and angiogenesis (5-10×), all related to cell-matrix interactions. Moreover, the HBM matrix affects osteoblast function. WT osteoblasts plated on HBM OI decellularized matrix in vitro showed less punctate vinculin, increased peripheral actin staining, and the presence of lamellipodia, suggesting a decrease in cellular adhesion. Insights into the mechanism of HBM OI mineralization may lead to improved therapies for HBM OI and low bone mass conditions.

Indexed as

Bone MatrixCalcification, PhysiologicCell DifferentiationOsteoblastsOsteogenesis ImperfectaAnimalsBone DensityDisease Models, AnimalHumansMiceOsteogenesis

Identifiers

PMID42297796
PMCPMC13269806

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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.