Evidence map›Paper›PMID 34403754›Full record

ArticleBone2021

Age-associated changes in microRNAs affect the differentiation potential of human mesenchymal stem cells: Novel role of miR-29b-1-5p expression.

Nada H Eisa, Periyasamy T Sudharsan, Sergio Mas Herrero, Samuel A Herberg, Brian F Volkman, Alexandra Aguilar-Pérez, Dmitry Kondrikov, Ahmed M Elmansi, Charles Reitman, Xingming Shi and 7 more

Open access · greenAbstract read
In one paragraph

Article in Bone, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 25% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Differential Responses to Aging Among the Transcriptome and Proteome of Mesenchymal Progenitor Populations.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. 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

17 authors at 7 institutions in 4 countries.

Nada H EisaDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29403, United States of America; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403, United States of America; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Periyasamy T SudharsanGeorgia Cancer Center, Augusta University, Augusta, GA 30912, United States of America; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.
Sergio Mas HerreroUniversitat de Barcelona, Unitat Farmacologia, Dpt. Fonaments Clínics, 08036 Barcelona, Spain.
Samuel A HerbergDepartments of Ophthalmology and Visual Sciences, and Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, United States of America.
Brian F VolkmanBiochemistry Department, Medical College of Wisconsin, Milwaukee, WI 53226, United States of America.
Alexandra Aguilar-PérezDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Department of Anatomy and Cell Biology, Indiana University School of Medicine in Indianapolis, IN, United States of America; Department of Cellular and Molecular Biology, School of Medicine, Universidad Central del Caribe, Bayamon 00956, Puerto Rico.
Dmitry KondrikovDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29403, United States of America; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403, United States of America.
Ahmed M ElmansiDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29403, United States of America; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403, United States of America.
Charles ReitmanDepartment of Orthopaedics and Physical Medicine, Medical University of South Carolina, Charleston, SC 29403, United States of America.
Xingming ShiDepartment of Orthopaedics and Physical Medicine, Medical University of South Carolina, Charleston, SC 29403, United States of America; Department of Orthopaedic Surgery, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Center for Healthy Aging, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.
Sadanand FulzeleDepartment of Orthopaedic Surgery, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Center for Healthy Aging, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.
Meghan E McGee-LawrenceDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Department of Orthopaedic Surgery, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Center for Healthy Aging, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.
Carlos M IsalesDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Department of Orthopaedic Surgery, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Division of Endocrinology, Diabetes and Metabolism, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.
Mark W HamrickDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Department of Orthopaedic Surgery, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Center for Healthy Aging, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.
Maribeth H JohnsonDepartment of Population Health Sciences, Division of Biostatistics and Data Science Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.
Jie ChenDepartment of Population Health Sciences, Division of Biostatistics and Data Science Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America.
William D HillDepartment of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29403, United States of America; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403, United States of America; Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America; Center for Healthy Aging, Medical College of Georgia, Augusta University, Augusta, GA 30912, United States of America. Electronic address: hillwi@musc.edu.
Augusta University · USMedical University of South Carolina · USRalph H. Johnson VA Medical Center · USCentral University of the Caribbean · PRMedical College of Wisconsin · USSUNY Upstate Medical University · USUniversitat de Barcelona · ES

Funding

THE LEPTIN-IGF1 AXIS IN MUSCULOSKELETAL AGINGP01AG036675 · NIA · AUGUSTA UNIVERSITY · PI Sadanand tukdoji Fulzele · 2011 to 2026
$31.5M
Research Training in BiogerontologyT32AG000114 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCOTT PLETCHER · 1985 to 2026
$12.4M
Structural Basis for Chemokine FunctionR37AI058072 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI Brian F Volkman · 2020 to 2026
$2.8M
Kynurenine Pathway Regulation of CNS Senescence in Alzheimer's Disease PathologyR01AG067510 · NIA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HILL, WILLIAM D, MCGEE-LAWRENCE, MEGHAN E. · 2020 to 2023
$2.4M
Blockade of miR-29b-1-5p promotes MSC-mediated bone regeneration during agingF32DE024712 · NIDCR · CASE WESTERN RESERVE UNIVERSITY · PI HERBERG, SAMUEL · 2014 to 2016
$166k
CSRD VA I01 CX000930NIAID NIH HHS R37 AI058072NIA NIH HHS P01 AG036675NIA NIH HHS R01 AG067510NIA NIH HHS T32 AG000114NIDCR NIH HHS F32 DE024712
6 · The paper itself

Abstract

Age-associated osteoporosis is widely accepted as involving the disruption of osteogenic stem cell populations and their functioning. Maintenance of the local bone marrow (BM) microenvironment is critical for regulating proliferation and differentiation of the multipotent BM mesenchymal stromal/stem cell (BMSC) population with age. The potential role of microRNAs (miRNAs) in modulating BMSCs and the BM microenvironment has recently gained attention. However, miRNAs expressed in rapidly isolated BMSCs that are naïve to the non-physiologic standard tissue culture conditions and reflect a more accurate in vivo profile have not yet been reported. Here we directly isolated CD271 positive (+) BMSCs within hours from human surgical BM aspirates without culturing and performed microarray analysis to identify the age-associated changes in BMSC miRNA expression. One hundred and two miRNAs showed differential expression with aging. Target prediction and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the up-regulated miRNAs targeting genes in bone development pathways were considerably enriched. Among the differentially up-regulated miRNAs the novel passenger strand miR-29b-1-5p was abundantly expressed as a mature functional miRNA with aging. This suggests a critical arm-switching mechanism regulates the expression of the miR-29b-1-5p/3p pair shifting the normally degraded arm, miR-29b-1-5p, to be the dominantly expressed miRNA of the pair in aging. The normal guide strand miR-29b-1-3p is known to act as a pro-osteogenic miRNA. On the other hand, overexpression of the passenger strand miR-29b-1-5p in culture-expanded CD271+ BMSCs significantly down-regulated the expression of stromal cell-derived factor 1 (CXCL12)/ C-X-C chemokine receptor type 4 (SDF-1(CXCL12)/CXCR4) axis and other osteogenic genes including bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (RUNX2). In contrast, blocking of miR-29b-1-5p function using an antagomir inhibitor up-regulated expression of BMP-2 and RUNX2 genes. Functional assays confirmed that miR-29b-1-5p negatively regulates BMSC osteogenesis in vitro. These novel findings provide evidence of a pathogenic anti-osteogenic role for miR-29b-1-5p and other miRNAs in age-related defects in osteogenesis and bone regeneration.

Indexed as

Mesenchymal Stem CellsMicroRNAsBone Marrow CellsCell DifferentiationHumansOsteogenesisMicroRNAsAgingCXCL12Human mesenchymal stem cellsmicroRNAOsteoporosisSDF-1

Identifiers

PMID34403754
PMCPMC8935397
OpenAlexW3194243476

What OpenQuestion holds

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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.