Evidence map›Paper›PMID 27563882›Full record

ArticleInternational journal of molecular sciences2016

Hypoxia Suppresses Spontaneous Mineralization and Osteogenic Differentiation of Mesenchymal Stem Cells via IGFBP3 Up-Regulation.

Ji Hye Kim, Sei Mee Yoon, Sun U Song, Sang Gyu Park, Won-Serk Kim, In Guk Park, Jinu Lee, Jong-Hyuk Sung

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 15% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
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  7. The role of IGF/IGF-1R signaling in the regulation of cancer stem cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 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

8 authors at 5 institutions in 2 countries.

Ji Hye KimCollege of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea. wisdom-ks@hanmail.net.
Sei Mee YoonCollege of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea. sei_mee@naver.com.
Sun U SongInha University School of Medicine, Translational Research Center and Inha Research, Institute for Medical Sciences, Incheon 21983, Korea. sunuksong@inha.ac.kr.
Sang Gyu ParkCollege of Pharmacy, Ajou University, Suwon 16499, Korea. sgpark@ajou.ac.kr.
Won-Serk KimDepartment of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03722, Korea. susini@naver.com.
In Guk ParkDepartment of Biochemistry, Stony Brook University, Stony Brook, NY 11790, USA. allpleache@naver.com.
Jinu LeeCollege of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea. jinulee@yonsei.ac.kr.
Jong-Hyuk SungCollege of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea. brian99@empal.com.
Yonsei University · KRAjou University · KRInha University · KRKangbuk Samsung Hospital · KRStony Brook University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia has diverse stimulatory effects on human adipose-derived stem cells (ASCs). In the present study, we investigated whether hypoxic culture conditions (2% O₂) suppress spontaneous mineralization and osteogenic differentiation of ASCs. We also investigated signaling pathways and molecular mechanisms involved in this process. We found that hypoxia suppressed spontaneous mineralization and osteogenic differentiation of ASCs, and up-regulated mRNA and protein expression of Insulin-like growth factor binding proteins (IGFBPs) in ASCs. Although treatment with recombinant IGFBPs did not affect osteogenic differentiation of ASCs, siRNA-mediated inhibition of IGFBP3 attenuated hypoxia-suppressed osteogenic differentiation of ASCs. In contrast, overexpression of IGFBP3 via lentiviral vectors inhibited ASC osteogenic differentiation. These results indicate that hypoxia suppresses spontaneous mineralization and osteogenic differentiation of ASCs via intracellular IGFBP3 up-regulation. We determined that reactive oxygen species (ROS) generation followed by activation of the MAPK and PI3K/Akt pathways play pivotal roles in IGFBP3 expression under hypoxia. For example, ROS scavengers and inhibitors for MAPK and PI3K/Akt pathways attenuated the hypoxia-induced IGFBP3 expression. Inhibition of Elk1 and NF-κB through siRNA transfection also led to down-regulation of IGFBP3 mRNA expression. We next addressed the proliferative potential of ASCs with overexpressed IGFBP3, but IGFBP3 overexpression reduced the proliferation of ASCs. In addition, hypoxia reduced the osteogenic differentiation of bone marrow-derived clonal mesenchymal stem cells. Collectively, our results indicate that hypoxia suppresses the osteogenic differentiation of mesenchymal stem cells via IGFBP3 up-regulation.

Indexed as

AnimalsCell DifferentiationCell HypoxiaCell ProliferationCells, CulturedHumansImmunoprecipitationInsulin-Like Growth Factor Binding Protein 3Mesenchymal Stem CellsMiceOsteogenesisReactive Oxygen SpeciesReal-Time Polymerase Chain ReactionInsulin-Like Growth Factor Binding Protein 3Reactive Oxygen Speciesadipose-derived stem cellshypoxiaIGFBP3osteogenic differentiationreactive oxygen species

Identifiers

PMID27563882
PMCPMC5037669
OpenAlexW2517214191

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.