Magnetic Nanocomposite Scaffold-Induced Stimulation of Migration and Odontogenesis of Human Dental Pulp Cells through Integrin Signaling Pathways
Authors: Jung-Ju Kim
Jung-Hwan Lee
Hyung-Mun Yun
Hae-Won Kim
Eun-cheol Kim
Kyung-Ran Park
Eui-Suk Lee
Mi-joo Kim
Jin-Kyu Yi
Hae-Hyoung Lee
Journal: PLoS ONE (2015)
Discipline: Multidisciplinary
Keywords: Magnetism; Nanocomposite scaffolds; Magnetite nanoparticles; Polycaprolactone; Human dental pulp cells
Affiliations: Department of Oral and Maxillofacial Pathology & Research Center for tooth and periodontal tissue regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Korea., Department of Oral and Maxillofacial Surgery, Guro Hospital, Korea University, Seoul, Republic of Korea., Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea., Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Republic of Korea., Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea., Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Republic of Korea.

Abstract:  Magnetism is an intriguing physical cue that can alter the behaviors of a broad range of cells. Nanocomposite scaffolds that exhibit magnetic properties are thus considered useful 3D matrix for culture of cells and their fate control in repair and regeneration processes. Here we produced magnetic nanocomposite scaffolds made of magnetite nanoparticles (MNPs) and polycaprolactone (PCL), and the effects of the scaffolds on the adhesion, growth, migration and odontogenic differentiation of human dental pulp cells (HDPCs) were investigated. Furthermore, the associated signaling pathways were examined in order to elucidate the molecular mechanisms in the cellular events. The magnetic scaffolds incorporated with MNPs at varying concentrations (up to 10%wt) supported cellular adhesion and multiplication over 2 weeks, showing good viability. The cellular constructs in the nanocomposite scaffolds played significant roles in the stimulation of adhesion, migration and odontogenesis of HDPCs. Cells were shown to adhere to substantially higher number when affected by the magnetic scaffolds. Cell migration tested by in vitro wound closure model was significantly enhanced by the magnetic scaffolds. Furthermore, odontogenic differentiation of HDPCs, as assessed by the alkaline phosphatase activity, mRNA expressions of odontogenic markers (DMP-1, DSPP,osteocalcin, and ostepontin), and alizarin red staining, was significantly stimulated by the magnetic scaffolds. Signal transduction was analyzed by RT-PCR, Western blotting, and confocal microscopy. The magnetic scaffolds upregulated the integrin subunits (Œ±1, Œ±2, Œ≤1 and Œ≤3) and activated downstream pathways, such as FAK, paxillin, p38, ERK MAPK, and NF-Œ∫B. The current study reports for the first time the significant impact of magnetic scaffolds in stimulating HDPC behaviors, including cell migration and odontogenesis, implying the potential usefulness of the magnetic scaffolds for dentin-pulp tissue engineering. 

Retracted: No

PubPeer comments:
 *[right]* Figure 5 from [Yi et al (2020)] .  Electron microscopic images showing induction of autophagy by Baicalein in MDA-T68 thyroid cancer cells in a dose-dependent manner (rectangular boxes indicate the autophagosomes). *[left]* Figure 2 from [Wen et al (2019)] .  Electron microscopy of the SCC-1 human oral squamous cancer cells treated with xanthoxyletin shows autophagy.  , 
 Figure 4.  Western blot analysis showing that Baicalein increases the expression of Bax and decreases the expression of Bcl-2 in MDA-T6 thyroid cancer cells dose-dependently .  For comparison: *[left]* Figure 5 from [Chen et al (2020)] .  Effect of indicated concentrations of 7-Methoxyheptaphylline on the expression of apoptosis-related proteins by western blot analysis. The Figure shows that the expression of Bax increased and that of Bcl-2 decreased upon 7-Methoxyheptaphylline treatment of the retinoblastoma cells . *[right]* Figure 8 from [Xu et al (2020)] .  Western blot analysis showing the effect of Shionone on the MEK ERK and STAT3 signalling pathway in SK-BR-3 cells. The Figure shows that the expression of p-ERK, p-MEK and p-STAT-3 decreases in a dose-dependent manner upon Shionone treatment .  , 
 This paper has undergone an unacknowledged revision or correction, replacing the problematic Figures 4 and 5. The new version currently available on the journal s website was created modified on 11 January 2021.  Interested readers can still consult the original version (created 20 February 2020), via a copy currently [archived at ResearchGate] .  , 
 The paper has reverted to its original version, and acquired a [May June Expression of Concern] .  Following the publication of this article [1], readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause. ,