Evidence map›Paper›PMID 31882321›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020

Coactivation of Endogenous Wnt10b and Foxc2 by CRISPR Activation Enhances BMSC Osteogenesis and Promotes Calvarial Bone Regeneration.

Mu-Nung Hsu, Kai-Lun Huang, Fu-Jen Yu, Po-Liang Lai, Anh Vu Truong, Mei-Wei Lin, Nuong Thi Kieu Nguyen, Chih-Che Shen, Shiaw-Min Hwang, Yu-Han Chang and 1 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

38 citing papers in PubMed, 64 citations in OpenAlex.

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  19. Enhanced Osteogenic Potential ofACS biomaterials science & engineering · 2023
    Article
  20. Progress and Perspective of CRISPR-Cas9 Technology in Translational Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
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

11 authors at 4 institutions in 1 country.

Mu-Nung HsuDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Kai-Lun HuangDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Fu-Jen YuDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Po-Liang LaiDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Linkou 333, Taiwan; Bone and Joint Research Center, Chang Gung Memorial Hospital, Linkou 333, Taiwan.
Anh Vu TruongDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Mei-Wei LinDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan; Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
Nuong Thi Kieu NguyenDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Chih-Che ShenDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Shiaw-Min HwangBioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan.
Yu-Han ChangDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Linkou 333, Taiwan; College of Medicine, Chang Gung University, Taoyuan 333, Taiwan. Electronic address: yhchang@cloud.cgmh.org.tw.
Yu-Chen HuDepartment of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, Taiwan. Electronic address: yuchen@che.nthu.edu.tw.
National Tsing Hua University · TWChang Gung Memorial Hospital · TWFood Industry Research and Development Institute · TWIndustrial Technology Research Institute · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR activation (CRISPRa) is a burgeoning technology for programmable gene activation, but its potential for tissue regeneration has yet to be fully explored. Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into osteogenic or adipogenic pathways, which are governed by the Wnt (Wingless-related integration site) signaling cascade. To promote BMSC differentiation toward osteogenesis and improve calvarial bone healing by BMSCs, we harnessed a highly efficient hybrid baculovirus vector for gene delivery and exploited a synergistic activation mediator (SAM)-based CRISPRa system to activate Wnt10b (that triggers the canonical Wnt pathway) and forkhead c2 (Foxc2) (that elicits the noncanonical Wnt pathway) in BMSCs. We constructed a Bac-CRISPRa vector to deliver the SAM-based CRISPRa system into rat BMSCs. We showed that Bac-CRISPRa enabled CRISPRa delivery and potently activated endogenous Wnt10b and Foxc2 expression in BMSCs for >14 days. Activation of Wnt10b or Foxc2 alone was sufficient to promote osteogenesis and repress adipogenesis in vitro. Furthermore, the robust and prolonged coactivation of both Wnt10b and Foxc2 additively enhanced osteogenic differentiation while inhibiting adipogenic differentiation of BMSCs. The CRISPRa-engineered BMSCs with activated Wnt10b and Foxc2 remarkably improved the calvarial bone healing after implantation into the critical-sized calvarial defects in rats. These data implicate the potentials of CRISPRa technology for bone tissue regeneration.

Indexed as

Transcriptional ActivationAdipogenesisAnimalsBone RegenerationCalcification, PhysiologicCalciumCell DifferentiationCells, CulturedForkhead Transcription FactorsMesenchymal Stem CellsOsteogenesisRatsSkullWnt ProteinsWnt Signaling PathwayX-Ray MicrotomographyCalciumForkhead Transcription Factorsmesenchyme fork head 1 proteinWnt10b protein, ratWnt Proteinsbaculovirusbone regenerationCRISPRaFoxc2gene activationWnt10b

Identifiers

PMID31882321
PMCPMC7001053
OpenAlexW2994006536

What OpenQuestion holds

Textmetadata
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.