<p>The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway</p>
Authors: Guilan Zhang
Longquan Shao
Yanli Zhang
Liangjiao Chen
Wenjing Liu
Hui Zhong
Aijie Chen
Ruolan Wang
Haiyun Luo
Journal: International Journal of Nanomedicine (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: BMSCs; Smad4; bone regeneration; osteogenic differentiation; tantalum nanoparticles.
Affiliations: Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China., Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangzhou 510515, People's Republic of China., Department of Prosthodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, People's Republic of China., Department of Orthodontics, Stomatological Hospital, Guangzhou Medical University, Guangzhou, 510150, People's Republic of China., Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou 510280, People's Republic of China.

Abstract:  Background: In recent years, nanomaterials have been increasingly developed and applied in the field of bone tissue engineering. However, there are few studies on the induction of bone regeneration by tantalum nanoparticles (Ta NPs) and no reports on the effects of Ta NPs on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanisms. The main purpose of this study was to investigate the effects of Ta NPs on bone regeneration and BMSC osteogenic differentiation and the underlying mechanisms. Materials and methods: The effects of Ta NPs on bone regeneration were evaluated in an animal experiment, and the effects of Ta NPs on osteogenic differentiation of BMSCs and the underlying mechanisms were evaluated in cell experiments. In the animal experiment, hematoxylin-eosin (HE) staining and hard-tissue section analysis showed that Ta NPs promoted bone regeneration, and immunohistochemistry revealed elevated expression of BMP2 and Smad4 in cells cultured with Ta NPs. Results: The results of the cell experiments showed that Ta NPs promoted BMSC proliferation, alkaline phosphatase (ALP) activity, BMP2 secretion and extracellular matrix (ECM) mineralization, and the expression of related osteogenic genes and proteins (especially BMP2, Smad4 and Runx2) was upregulated under culture with Ta NPs. Smad4 expression, ALP activity, ECM mineralization, and osteogenesis-related gene and protein expression decreased after inhibiting Smad4. Conclusion: These data suggest that Ta NPs have an osteogenic effect and induce bone regeneration by activating the BMP2/Smad4/Runx2 signaling pathway, which in turn causes BMSCs to undergo osteogenic differentiation. This study provides insight into the molecular mechanisms underlying the effects of Ta NPs in bone regeneration. 

Retracted: Yes

PubPeer comments:
 Figure 5 appears to have two images which overlap. Annotated in green. *** ![file] , 
 More overlap annotated in blue yellow. ![file] , 
 #2 ![file] , 
 Thank you for your comments. As for the problem of graph, the explanation is as follows. First of all, this is a continuous experiment. The same batch of samples may be observed and photographed many times, and the same sample will be photographed many times in a row (this is a repetitive experiment). I will explain with this journal and attach the results of repeated experiments. We will continue with the journal, and we will supplement this part of the relevant experimental data. , 
 #2 Thank you for your comments. As for the problem of graph, the explanation is as follows. First of all, this is a continuous experiment. The same batch of samples may be observed and photographed many times, and the same sample will be photographed many times in a row (this is a repetitive experiment). I will explain with this journal and attach the results of repeated experiments. We will continue with the journal, and we will supplement this part of the relevant experimental data. , 
 #5 u201cThe same batch of samples may be observed and photographed many times.u201d While this may be true, the same sample should not have been treated one way and photographed, then treated differently and photographed again, as appears to have been done with the samples marked in green in Figure 5B. Additionally, the scale bars and legend in 5B appear to indicate all samples were photographed at the same scale, yet the images indicated with black, blue, and yellow boxes in the bottom row all appear to be close-up images of the top row. It will be interesting to see how the Editor in Charge responds to your explanation. , 
 #5 *The same batch of samples may be observed and photographed many times, and the same sample will be photographed many times in a row (this is a repetitive experiment).* The key words here are  same sample . A sample that is 20 microg-g mL at Day 14 cannot become a 15 microg-g mL sample at Day 21 (at twice the scale). , 
 #7 #6 Thank you for your comments, which will be communicated to the journal later. It may be because of the operation that the graph is misused. At the same time, I have been doing relevant research experiments. I will not exclude to supplement this part of experimental data in the future. Thank you for your attention! , 
 I applaud the authors for their fast reply but, as pointed out by Actinopolyspora and Hoya, their comments do not make much sense, scientifically. The possible overlaps are observed between samples that received different treatments and that were fixed and stained, so these cannot be photos taken of the same sample. In addition to the concerns posted above, I would like to point out some possible overlap between panels in Figure 5A and 7A, marked here in orange and green boxes. There might be more. I look forward to the authors response. ![file] , 
 Figure 5G and 7G: *Pink boxes: The 15 ug ml panels in Figure 5G appear to look similar to the 0 ug ml panels in Figure 7G. ![file] , 
 #9 Thank you for your comments. I ll take a closer look at the results of my experiment. If it s an operational error, I will contact the journal immediately to make corrections. If it s the problem of the experiment itself, I d like to add some experimental data again. Thank you for your attention! , 
 May 8, 2020 retraction notice here: https: www.dovepress.com retraction-the-role-of-tantalum-nanoparticles-in-bone-regeneration-inv-peer-reviewed-article-IJN It reads:  The Editor-in-Chief and Publisher of International Journal of Nanomedicine wish to retract the published article. We were notified of potential image duplications found in the published article. The alleged image duplications are: u25cf Figure 5A 7 days Panel 15 u03bcg mL shares parts of the same image shown in Figure 7A 7 days Panel 20 u03bcg mL+inhibitor u25cf Figure 5A 14 days Panel 25 u03bcg mL shares parts of the same image shown in Figure 7A 14 days Panel 20 u03bcg mL+inhibitor u25cf Figure 5B 14 days Panel 15 u03bcg mL shares parts of the same image shown in Figure 5B 21 days Panel 0 u03bcg mL which has also been magnified u25cf Figure 5B 14 days Panel 20 u03bcg mL shares parts of the same images shown in Figure 5B 21 days Panels 15 u03bcg mL and 20 u03bcg mL, both of which have also been magnified u25cf Figure 5B 21 days Panel 5 u03bcg mL shares parts of the same image shown in Figure 5B 21 days Panel 10 u03bcg mL u25cf Figure 5G DAPI, FITC, Merge Panel 15 u03bcg mL are the same images shown in Figure 7G DAPI, FITC, Merge Panel 0 u03bcg mL The authors could not provide a satisfactory explanation for the duplicated images and the editor determined the findings of the study were no longer valid. The authors wish to apologize for this error. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,