Evidence map›Paper›PMID 34585526›Full record

ArticleAdvanced healthcare materials2021

β-Catenin Limits Osteogenesis on Regenerative Materials in a Stiffness-Dependent Manner.

Qi Zhou, Xiaoyan Ren, Michelle K Oberoi, Meiwand Bedar, Rachel M Caprini, Marley J Dewey, Vasiliki Kolliopoulos, Dean T Yamaguchi, Brendan A C Harley, Justine C Lee

Open access · greenAbstract read
In one paragraph

Article in Advanced healthcare materials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

17 citing papers in PubMed, 23 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 3 institutions in 1 country.

Qi ZhouDivision 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.
Michelle K OberoiDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
Meiwand BedarDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
Rachel M CapriniDivision of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
Marley J DeweyDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Vasiliki KolliopoulosDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Dean T YamaguchiResearch Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA, 90073, 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 · USVA Greater Los Angeles Healthcare System · 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
Osteoclast modulatory biomaterials for skull regenerationR01DE029234 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEE, JUSTINE CHIA · 2020 to 2024
$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
NIDCR NIH HHS R01 DE028098NIDCR NIH HHS R01 DE029234NIDCR NIH HHS R21 DE026582
6 · The paper itself

Abstract

Targeted refinement of regenerative materials requires mechanistic understanding of cell-material interactions. The nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffold is shown to promote skull regeneration in vivo without additive exogenous growth factors or progenitor cells, suggesting potential for clinical translation. This work evaluates modulation of MC-GAG stiffness on canonical Wnt (cWnt) signaling. Primary human bone marrow-derived mesenchymal stem cells (hMSCs) are differentiated on two MC-GAG scaffolds (noncrosslinked, NX-MC, 0.3 kPa vs conventionally crosslinked, MC, 3.9 kPa). hMSCs increase expression of activated β-catenin, the major cWnt intracellular mediator, and the mechanosensitive YAP protein with near complete subcellular colocalization on stiffer MC scaffolds. Overall Wnt pathway inhibition reduces activated β-catenin and osteogenic differentiation, while elevating BMP4 and phosphorylated Smad1/5 (p-Smad1/5) expression on MC, but not NX-MC. Unlike Wnt pathway downregulation, isolated canonical Wnt inhibition with β-catenin knockdown increases osteogenic differentiation and mineralization specifically on the stiffer MC. β-catenin knockdown also increases p-Smad1/5, Runx2, and BMP4 expression only on the stiffer MC material. Thus, while stiffness-induced activation of the Wnt and mechanotransduction pathways promotes osteogenesis on MC-GAG, activated β-catenin is a limiting agent and may serve as a useful target or readout for optimal modulation of stiffness in skeletal regenerative materials.

Indexed as

Mesenchymal Stem CellsOsteogenesisbeta CateninCell DifferentiationCells, CulturedHumansMechanotransduction, CellularWnt Signaling Pathwaybeta CateninCTNNB1 protein, humanbeta-cateninbone regenerationnanoparticulate mineralized collagen glycosaminoglycanstiffnessWnt

Identifiers

PMID34585526
PMCPMC8665088
OpenAlexW3203289379

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.