Evidence map›Paper›PMID 35950212›Full record

ArticleMolecular therapy. Nucleic acids2022

AAV-mediated delivery of osteoblast/osteoclast-regulating miRNAs for osteoporosis therapy.

Aijaz Ahmad John, Jun Xie, Yeon-Suk Yang, Jung-Min Kim, Chujiao Lin, Hong Ma, Guangping Gao, Jae-Hyuck Shim

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

20 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
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  11. Beyond resorption: osteoclasts as drivers of bone formation.Cell regeneration (London, England) · 2024
    Review
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  16. Nucleic Acid Aptamers Protect Against Lead (Pb(II)) Toxicity.bioRxiv : the preprint server for biology · 2024
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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

8 authors at 1 institution in 1 country.

Aijaz Ahmad JohnDepartment of Medicine, Division of Rheumatology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Jun XieHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Yeon-Suk YangDepartment of Medicine, Division of Rheumatology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Jung-Min KimDepartment of Medicine, Division of Rheumatology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Chujiao LinDepartment of Medicine, Division of Rheumatology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Hong MaHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Guangping GaoHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Jae-Hyuck ShimDepartment of Medicine, Division of Rheumatology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
University of Massachusetts Chan Medical School · US

Funding

Viral escape from AAV expressed transgenesP01AI100263 · NIAID · SCRIPPS FLORIDA · PI GAO, GUANGPING · 2012 to 2016
$11.9M
Tech-CoreP01HD080642 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DIMAURO, SALVATORE, HIRANO, MICHIO · 2014 to 2018
$7.8M
Translational Imaging and Phenotyping CoreP30AR075042 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI Marie Demay · 2019 to 2026
$7.4M
Oligodendrocyte-focused rAAV gene therapy strategies for Canavan disease and LeukodystrophiesR01NS076991 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Guangping Gao · 2012 to 2026
$5.7M
Novel approaches to promote healing of bone loss in inflammatory arthritisR01AR078230 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Ellen M Gravallese, Jae-Hyuck Shim · 2022 to 2026
$2.6M
A novel bone-targeting AAV-mediated gene therapy to promote bone formation in osteoporosisR21AR077557 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SHIM, JAE-HYUCK · 2021 to 2022
$403k
NIAID NIH HHS P01 AI100263NIAMS NIH HHS R01 AR078230NIAMS NIH HHS R21 AR077557NICHD NIH HHS P01 HD080642NINDS NIH HHS R01 NS076991
6 · The paper itself

Abstract

Osteoporosis occurs due to a dysregulation in bone remodeling, a process requiring both bone-forming osteoblasts and bone-resorbing osteoclasts. Current leading osteoporosis therapies suppress osteoclast-mediated bone resorption but show limited therapeutic effects because osteoblast-mediated bone formation decreases concurrently. We developed a gene therapy strategy for osteoporosis that simultaneously promotes bone formation and suppresses bone resorption by targeting two microRNAs (miRNAs)-miR-214-3p and miR-34a-5p. We modulated the expression of these miRNAs using systemically delivered recombinant adeno-associated viral (rAAV) vectors targeting the bone. rAAV-mediated overexpression of miR-214-3p or inhibition of miR-34a-5p in the skeleton resulted in bone loss in adult mice, resembling osteoporotic bones. Conversely, rAAV-mediated inhibition of miR-214-3p or overexpression of miR-34a-5p reversed bone loss in mouse models for postmenopausal and senile osteoporosis by increasing osteoblast-mediated bone formation and decreasing osteoclast-mediated bone resorption. Notably, these mice did not show any apparent pathological phenotypes in non-skeletal tissues. Mechanistically, inhibiting miR-214-3p upregulated activating transcription factor 4 in osteoblasts and phatase and tensin homolog in osteoclasts, while overexpressing miR-34a-5p downregulated Notch1 in osteoblasts and TGF-β-induced factor homeobox 2 in osteoclasts. In summary, bone-targeting rAAV-mediated regulation of miR-214-3p or miR-34a-5p is a promising new approach to treat osteoporosis, while limiting adverse effects in non-skeletal tissues.

Indexed as

bonemiR-214-3pmiR-34a-5posteoblastosteoclastosteoporosisrAAVtough decoys

Identifiers

PMID35950212
PMCPMC9352805
OpenAlexW4285010837

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.