Evidence map›Paper›PMID 37088847›Full record

ArticleJournal of biomedical science2023

Downregulation of the RNA-binding protein PUM2 facilitates MSC-driven bone regeneration and prevents OVX-induced bone loss.

Dong Suk Yoon, Yoorim Choi, Kyoung-Mi Lee, Eun Ae Ko, Eun-Ji Kim, Kwang Hwan Park, Jin Woo Lee

Open access · diamondAbstract read
In one paragraph

Article in Journal of biomedical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.3field-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

10 citing papers in PubMed, 15 citations in OpenAlex.

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  10. RNA-binding proteins in bone pathophysiology.Frontiers in cell and developmental biology · 2024
    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

7 authors at 1 institution in 1 country.

Dong Suk Yoon *Department of Biomedical Science, Hwasung Medi-Science University, Hwaseong-Si 18274, Gyeonggi-Do, South Korea.
Yoorim Choi *Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Kyoung-Mi Lee *Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Eun Ae KoDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Eun-Ji KimDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Kwang Hwan ParkDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Jin Woo LeeDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea. ljwos@yuhs.ac.
Yonsei University · KR

Funding

National Research Foundation of Korea NRF-2021R1C1C2093717
6 · The paper itself

Abstract

backgroundAlthough mRNA dysregulation can induce changes in mesenchymal stem cell (MSC) homeostasis, the mechanisms by which post-transcriptional regulation influences MSC differentiation potential remain understudied. PUMILIO2 (PUM2) represses translation by binding target mRNAs in a sequence-specific manner.

methodsIn vitro osteogenic differentiation assays were conducted using human bone marrow-derived MSCs. Alkaline phosphatase and alizarin red S staining were used to evaluate the osteogenic potential of MSCs. A rat xenograft model featuring a calvarial defect to examine effects of MSC-driven bone regeneration. RNA-immunoprecipitation (RNA-IP) assay was used to determine the interaction between PUM2 protein and Distal-Less Homeobox 5 (DLX5) mRNA. Ovariectomized (OVX) mice were employed to evaluate the effect of gene therapy for postmenopausal osteoporosis.

resultsHere, we elucidated the molecular mechanism of PUM2 in MSC osteogenesis and evaluated the applicability of PUM2 knockdown (KD) as a potential cell-based or gene therapy. PUM2 level was downregulated during MSC osteogenic differentiation, and PUM2 KD enhanced MSC osteogenic potential. Following PUM2 KD, MSCs were transplanted onto calvarial defects in 12-week-old rats; after 8 weeks, transplanted MSCs promoted bone regeneration. PUM2 KD upregulated the expression of DLX5 mRNA and protein and the reporter activity of its 3'-untranslated region. RNA-IP revealed direct binding of PUM2 to DLX5 mRNA. We then evaluated the potential of adeno-associated virus serotype 9 (AAV9)-siPum2 as a gene therapy for osteoporosis in OVX mice.

conclusionOur findings suggest a novel role for PUM2 in MSC osteogenesis and highlight the potential of PUM2 KD-MSCs in bone regeneration. Additionally, we showed that AAV9-siPum2 is a potential gene therapy for osteoporosis.

Indexed as

Mesenchymal Stem CellsOsteoporosisAnimalsBone RegenerationCell DifferentiationCells, CulturedDown-RegulationHumansMiceOsteogenesisRatsRNARNA-Binding ProteinsRNA, MessengerPUM2 protein, humanPum2 protein, mouseRNARNA-Binding ProteinsRNA, MessengerBone regenerationGene therapyMesenchymal stem cellsOsteoporosisPUMILIO2

Identifiers

PMID37088847
PMCPMC10122812
OpenAlexW4366782297

What OpenQuestion holds

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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.