Evidence map›Paper›PMID 30898695›Full record

ArticleBone2019

MicroRNA-181a/b-1 over-expression enhances osteogenesis by modulating PTEN/PI3K/AKT signaling and mitochondrial metabolism.

Hongjun Zheng, Jin Liu, Eric Tycksen, Ryan Nunley, Audrey McAlinden

Open access · greenAbstract read
In one paragraph

Article in Bone, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

53 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
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  10. Circulating miRNAs are associated with successful bone regeneration.Frontiers in bioengineering and biotechnology · 2025
    Article
  11. Article
  12. Expert opinion on therapeutic targets · 2024
    Review
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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

5 authors at 2 institutions in 1 country.

Hongjun ZhengDepartment of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, United States of America. Electronic address: zheng.h@wustl.edu.
Jin LiuDepartment of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, United States of America. Electronic address: jin.liu@wustl.edu.
Eric TycksenGenome Technology Access Center, Washington University School of Medicine, St Louis, MO, United States of America. Electronic address: etycksen@wustl.edu.
Ryan NunleyDepartment of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, United States of America. Electronic address: nunleyr@wustl.edu.
Audrey McAlindenDepartment of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, United States of America; Department of Cell Biology, Washington University School of Medicine, St. Louis, MO, United States of America; Shriners Hospital for Children - St Louis, St Louis, MO, United States of America. Electronic address: mcalindena@wustl.edu.
Washington University in St. Louis · USShriners Hospitals for Children - St. Louis · US

Funding

The Role of the Osteoblast Secretome in Bone FormationP30AR057235 · NIAMS · WASHINGTON UNIVERSITY · PI SILVA, MATTHEW J · 2009 to 2018
$5.7M
Epigenetic Regulation in Cartilage TissueR01AR069605 · NIAMS · WASHINGTON UNIVERSITY · PI Regis J O'Keefe · 2016 to 2026
$3.5M
Regulation of Skeletal Development by microRNAsR01AR064191 · NIAMS · WASHINGTON UNIVERSITY · PI MCALINDEN, AUDREY · 2014 to 2018
$1.7M
Regulation of Chondrogenesis by Long Non-Coding RNAsR21AR072193 · NIAMS · WASHINGTON UNIVERSITY · PI MCALINDEN, AUDREY · 2018 to 2019
$369k
NIAMS NIH HHS P30 AR057235NIAMS NIH HHS R01 AR064191NIAMS NIH HHS R01 AR069605NIAMS NIH HHS R21 AR072193
6 · The paper itself

Abstract

MicroRNAs are small non-coding RNAs that play important roles in many cellular processes including proliferation, metabolism and differentiation. They function by binding to specific regions within the 3'UTR of target mRNAs resulting in suppression of protein synthesis and modulation of potentially many cellular pathways. We previously showed that miRNA expression levels differed between cells from distinct regions of developing human embryonic long bones. Specifically, we found that miR-181a-1 was significantly more highly expressed in hypertrophic chondrocytes compared to proliferating differentiated or progenitor chondrocytes, suggesting a potential role in regulating chondrocyte hypertrophy and/or endochondral bone formation. The goal of this study was to determine how miR-181a-1 together with its clustered miRNA, miR-181b-1, regulates osteogenesis. We show that over-expression of the miR-181a/b-1 cluster enhanced osteogenesis and that cellular pathways associated with protein synthesis and mitochondrial metabolism were significantly up-regulated. Metabolic assays revealed that the oxygen consumption rate and ATP-linked respiration were increased by miR-181a/b-1. To further decipher a potential mechanism causing these metabolic changes, we showed that PTEN (phosphatase and tensin homolog) levels were suppressed following miR-181a/b-1 over-expression, and that PI3K/AKT signaling was subsequently increased. Over-expression of PTEN was found to attenuate the enhancing effects of miR-181a/b-1, providing further evidence that miR-181a/b-1 regulates the PTEN/PI3K/AKT axis to enhance osteogenic differentiation and mitochondrial metabolism. These findings have important implications for the design of miR-181a/b targeting strategies to treat bone conditions such as fractures or heterotopic ossification.

Indexed as

Cell LineCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansKnee JointMicroRNAsMitochondriaOsteogenesisPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseRNA, Small UntranslatedSignal TransductionMicroRNAsMIrn181 microRNA, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, humanRNA, Small UntranslatedmicroRNAmiR-181a/bMitochondrial metabolismOsteogenesisPI3K/AKTPTEN

Identifiers

PMID30898695
PMCPMC6491221
OpenAlexW2923809108

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.