Transforming growth factor-β1 up-regulates connexin43 expression in osteocytes via canonical Smad-dependent signaling pathway
Authors: Jing Xie
Jianxun Sun
Xuedong Zhou
Yujia Cui
Linyi Cai
Wenjing Liu
Journal: Bioscience reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Connexin 43; Gap junction; Osteocyte; Smad3; Smad4
Affiliations: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China., State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China  (.

Abstract:  Connexin 43 (Cx43)-mediated gap junctional intercellular communication (GJIC) has been shown to be important in regulating multiple functions of bone cells. Transforming growth factor-β1 (TGF-β1) exhibited controversial effects on the expression of Cx43 in different cell types. To date, the effect of TGF-β1 on the Cx43 expression of osteocytes is still unknown. In the present study, we detected the expression of TGF-β1 in osteocytes and bone tissue, and then used recombinant mouse TGF-β1 to elucidate its effect on gap junctions (GJs) of osteocytes. Our data indicated that TGF-β1 up-regulated both mRNA and protein expression of Cx43 in osteocytes. Together with down-regulation of Cx43 expression after being treated with TGF-β type I receptor inhibitor Repsox, we deduced that TGF-β1 can positively regulate Cx43 expression in osteocytes. Thus we next focussed on the downstream signals of TGF-β and found that TGF-β1-mediated smads, Smad3 and Smad4, to translocate into nucleus. These translocated signal proteins bind to the promoter of Gja1 which was responsible for the changed expression of Cx43. The present study provides evidence that TGF-β1 can enhance GJIC between osteocytes through up-regulating Cx43 expression and the underlying mechanism involved in the activation of Smad-dependent pathway. 

Retracted: No

PubPeer comments:
 Two images in figure 2(A) appear to overlap when one is flipped horizontally and vertically. *** ![file] *** Showing original placement ![file] , 
 https: doi.org 10.1042 BSR-20181678_EOC The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 Thank you for your concern and correction. We have contacted the Editorial Office for this issue. Thank you again. , 
 #3 Thank you for your reply. Could you please post here the correct data? , 
 Yes, of course. we here provide the corrected version below which has been submitted to the Editorial Office. If you want to see the figure processing of picture misuse at that time, we can also provide it. Again, thank you for your correction. ![file] , 
 https: portlandpress.com bioscirep article 40 10 BSR-20181678_COR 226686 Correction-Transforming-growth-factor-1-up This Correction follows an Expression of Concern relating to this article previously published by Portland Press. The authors would like to make two corrections to their original article u201cTransforming growth factor-u03b21 up-regulates connexin43 expression in osteocytes via canonical Smad-dependent signaling pathwayu201d (Biosci Rep (2018) 38 (6): BSR20181678, DOI: https: doi.org 10.1042 BSR20181678). In Figure 2A, the authors would like to replace the cell image at 5 ng ml (0h) with the corrected one presented here. In the original version (at 5 ng ml, 0h) the image from the control group was used in error. ![file] In Figure 6D, the authors would like to replace the cell image of control group with the corrected one. In the original version of the Figure 6D, the image used in the Ctrl;Smad4 panel does not correspond to Smad4. The correct image from their reserved original data is used in the updated Figure 6 presented in this correction article. ![file] The authors claim that these corrections do not affect the conclusions of this article. The authors also apologise for any inconvenience that these errors have caused to the readers of the paper. ,