Evidence map›Paper›PMID 33919218›Full record

ArticleInternational journal of molecular sciences2021

Metallothionein 3 Promotes Osteoblast Differentiation in C2C12 Cells via Reduction of Oxidative Stress.

Santie Li, Myeong-Ji Kim, Sung-Ho Lee, Litai Jin, Weitao Cong, Hye-Gwang Jeong, Kwang-Youl Lee

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
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  7. Nrf2 signaling pathway: focus on oxidative stress in osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025
    Review
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  20. Osteoclastogenesis and Osteogenesis.International journal of molecular sciences · 2022
    Article
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 3 institutions in 2 countries.

Santie LiCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju 61186, Korea.
Myeong-Ji KimCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju 61186, Korea.
Sung-Ho LeeCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju 61186, Korea.ORCID 0000-0002-4654-384X
Litai JinSchool of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, China.
Weitao CongSchool of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, China.
Hye-Gwang JeongCollege of Pharmacy, Chungnam National University, Daejeon 34134, Korea.ORCID 0000-0002-8020-8914
Kwang-Youl LeeCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju 61186, Korea.
Chonnam National University · KRWenzhou Medical University · CNChungnam National University · KR

Funding

National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) 2019R1A5A2027521
6 · The paper itself

Abstract

Metallothioneins (MTs) are intracellular cysteine-rich proteins, and their expressions are enhanced under stress conditions. MTs are recognized as having the ability to regulate redox balance in living organisms; however, their role in regulating osteoblast differentiation is still unclear. In this research, we found that the expression of MT3, one member of the MT protein family, was specifically upregulated in the differentiation process of C2C12 myoblasts treated with bone morphogenetic protein 4 (BMP4). Transfection with MT3-overexpressing plasmids in C2C12 cells enhanced their differentiation to osteoblasts, together with upregulating the protein expression of bone specific transcription factors runt-related gene 2 (Runx2), Osterix, and distal-less homeobox 5 (Dlx5). Additionally, MT3 knockdown performed the opposite. Further studies revealed that overexpression of MT3 decreased reactive oxygen species (ROS) production in C2C12 cells treated with BMP4, and MT3 silencing enhanced ROS production. Treating C2C12 cells with antioxidant N-acetylcysteine also promoted osteoblast differentiation, and upregulated Runx2/Osterix/Dlx5, while ROS generator antimycin A treatment performed the opposite. Finally, antimycin A treatment inhibited osteoblast differentiation and Runx2/Osterix/Dlx5 expression in MT3-overexpressing C2C12 cells. These findings identify the role of MT3 in osteoblast differentiation and indicate that MT3 may have interesting potential in the field of osteogenesis research.

Indexed as

Cell DifferentiationGene Expression RegulationOsteogenesisOxidative StressAnimalsBone Morphogenetic Protein 4Cells, CulturedMetallothionein 3MiceMyoblastsNerve Tissue ProteinsOsteoblastsBmp4 protein, mouseBone Morphogenetic Protein 4Metallothionein 3Mt3 protein, mouseNerve Tissue Proteinsdistal-less homeobox 5metallothinnein 3osteoblast differentiationosterixoxidative stressrunt-related gene 2

Identifiers

PMID33919218
PMCPMC8122383
OpenAlexW3155553985

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.