Evidence map›Paper›PMID 33382197›Full record

ArticleMacromolecular bioscience2021

Stiffness of Nanoparticulate Mineralized Collagen Scaffolds Triggers Osteogenesis via Mechanotransduction and Canonical Wnt Signaling.

Qi Zhou, Shengyu Lyu, Anthony A Bertrand, Allison C Hu, Candace H Chan, Xiaoyan Ren, Marley J Dewey, Aleczandria S Tiffany, Brendan A C Harley, Justine C Lee

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

Article in Macromolecular bioscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

42 citing papers in PubMed, 43 citations in OpenAlex.

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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

10 authors at 2 institutions in 1 country.

Qi ZhouDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
Shengyu LyuDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
Anthony A BertrandDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
Allison C HuDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
Candace H ChanDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
Xiaoyan RenDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
Marley J DeweyDepartment of Materials Science and Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Aleczandria S TiffanyDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Brendan A C HarleyDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Justine C LeeDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.ORCID 0000-0002-8943-0837
University of California, Los Angeles · USUniversity of Illinois Urbana-Champaign · US

Funding

PRECLINICAL EVALUATION OF NANOPARTICULATE MINERALIZED COLLAGEN GLYCOSAMINOGLYCAN MATERIALS IN CALVARIAL REGENERATIONR01DE028098 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEE, JUSTINE CHIA · 2019 to 2023
$1.9M
Amniotic Membrane Derived Matrix for Large Bone Defect RepairR21DE026582 · NIDCR · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI HARLEY, BRENDAN A., WHEELER, MATTHEW B · 2018 to 2019
$660k
Human Bone Engineering and Resorption in a Novel Mineralized Collagen ScaffoldIK2BX002442 · VA · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · PI LEE, JUSTINE CHIA · 2015 to 2019
–
BLRD VA IK2 BX002442NIDCR NIH HHS R01 DE028098NIDCR NIH HHS R21 DE026582
6 · The paper itself

Abstract

The ability of the extracellular matrix (ECM) to instruct progenitor cell differentiation has generated excitement for the development of materials-based regenerative solutions. Described a nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) material capable of inducing in vivo skull regeneration without exogenous growth factors or ex vivo progenitor cell-priming is described previously. Here, the contribution of titrating stiffness to osteogenicity is evaluated by comparing noncrosslinked (NX-MC) and crosslinked (MC) forms of MC-GAG. While both materials are osteogenic, MC demonstrates an increased expression of osteogenic markers and mineralization compared to NX-MC. Both materials are capable of autogenously activating the canonical BMPR signaling pathway with phosphorylation of Smad1/5. However, unlike NX-MC, human mesenchymal stem cells cultured on MC demonstrate significant elevations in the major mechanotransduction mediators YAP and TAZ expression, coincident with β-catenin activation in the canonical Wnt signaling pathway. Inhibition of YAP/TAZ activation reduces osteogenic expression, mineralization, and β-catenin activation in MC, with less of an effect on NX-MC. YAP/TAZ inhibition also results in a reciprocal increase in Smad1/5 phosphorylation and BMP2 expression. The results indicate that increasing MC-GAG stiffness induces osteogenic differentiation via the mechanotransduction mediators YAP/TAZ and the canonical Wnt signaling pathway, whereas the canonical BMPR signaling pathway is activated independent of stiffness.

Indexed as

Mechanotransduction, CellularOsteogenesisWnt Signaling PathwayActinsAdaptor Proteins, Signal Transducingbeta CateninBone Morphogenetic Protein 2Bone Morphogenetic Protein ReceptorsCell NucleusCollagenCore Binding Factor Alpha 1 SubunitCross-Linking ReagentsCytosolFocal Adhesion Protein-Tyrosine KinasesGene Expression RegulationGlycosaminoglycansActinsAdaptor Proteins, Signal Transducingbeta CateninBone Morphogenetic Protein 2Bone Morphogenetic Protein ReceptorsCollagenCore Binding Factor Alpha 1 SubunitCross-Linking ReagentsFocal Adhesion Protein-Tyrosine KinasesGlycosaminoglycansIntegrinsIntracellular Signaling Peptides and ProteinsMineralsProtein Subunitsrho GTP-Binding ProteinsSmad ProteinsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsWWTR1 protein, humanYAP1 protein, humanYAP-Signaling ProteinsmechanotransductionscaffoldsWntYAP/TAZβ-catenin

Identifiers

PMID33382197
PMCPMC7977493
OpenAlexW3116004758

What OpenQuestion holds

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Registered trials

None linked

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.