Evidence map›Paper›PMID 34185419›Full record

ArticleClinical and translational medicine2021

IRF2-mediated upregulation of lncRNA HHAS1 facilitates the osteogenic differentiation of bone marrow-derived mesenchymal stem cells by acting as a competing endogenous RNA.

Guiwen Ye, Peng Wang, Zhongyu Xie, Jinteng Li, Guan Zheng, Wenjie Liu, Qian Cao, Ming Li, Shuizhong Cen, Zhaofeng Li and 3 more

Open access · goldAbstract read
In one paragraph

Article in Clinical and translational medicine, 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
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

17 citing papers in PubMed, 28 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

13 authors at 1 institution in 1 country.

Guiwen YeDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.
Peng WangDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.
Zhongyu XieDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.
Jinteng LiDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.
Guan ZhengDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.
Wenjie LiuDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.
Qian CaoCenter for Biotherapy, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.
Ming LiDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
Shuizhong CenDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
Zhaofeng LiDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
Wenhui YuDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.
Yanfeng WuCenter for Biotherapy, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.
Huiyong ShenDepartment of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, P.R. China.ORCID 0000-0002-4317-3468
Sun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMesenchymal stem cells (MSCs) are the major source of osteoblasts. Long noncoding RNAs (lncRNAs) are abundantly expressed RNAs that lack protein-coding potential and play an extensive regulatory role in cellular biological activities. However, the regulatory network of lncRNAs in MSC osteogenesis needs further investigation.

methodsQRT-PCR, western blot, immunofluorescence, and immunohistochemistry assays were used to determine the levels of relevant genes. The osteogenic differentiation capability was evaluated by using Alizarin Red S (ARS) staining, alkaline phosphatase activity assays, hematoxylin & eosin staining or micro-CT. RNA fluorescence in situ hybridization (FISH) and RNAscope were used to detect HHAS1 expression in cells and bone tissue. A microarray assay was performed to identify differentially expressed microRNAs. RNA immunoprecipitation and RNA pull-down were used to explore the interactions between related proteins and nucleic acids.

resultsThe level of lncRNA HHAS1 increased during bone marrow-derived MSC (BMSC) osteogenesis and was positively related to the levels of osteogenic genes and ARS intensity. HHAS1 was located in both the cytoplasm and the nucleus and was expressed in human bone tissue. HHAS1 facilitated BMSC osteogenic differentiation by downregulating miR-204-5p expression and enhancing the level of RUNX family transcription factor 2 (RUNX2). In addition, interferon regulatory factor 2 (IRF2) was increased during BMSC osteogenic differentiation and interacted with the promoter of HHAS1, which resulted in the transcriptional activation of HHAS1. Furthermore, IRF2 and HHAS1 helped improve bone defect repair in vivo.

conclusionsOur study identified a novel lncRNA, HHAS1, that facilitates BMSC osteogenic differentiation and proposed a role for the IRF2/HHAS1/miR-204-5p/RUNX2 axis in BMSC osteogenesis regulation. These findings help elucidate the regulatory network of BMSC osteogenesis and provide potential targets for clinical application.

Indexed as

OsteogenesisAnimalsCell DifferentiationCore Binding Factor Alpha 1 SubunitFractures, BoneHumansInterferon Regulatory Factor-2Mesenchymal Stem CellsMesenchymal Stem Cell TransplantationMiceMice, Inbred C57BLMicroRNAsOsteoblastsRNA, Long NoncodingCore Binding Factor Alpha 1 SubunitInterferon Regulatory Factor-2IRF2 protein, humanMicroRNAsMIRN204 microRNA, humanRNA, Long NoncodingRUNX2 protein, humanIRF2long noncoding RNAsmesenchymal stem cellsosteogenic differentiation

Identifiers

PMID34185419
PMCPMC8214856
OpenAlexW3173186344

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LicenceCC BY
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Registered trials

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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.