Home Life Sciences Hypoxia-induced microRNA-146a represses Bcl-2 through Traf6/IRAK1 but not Smad4 to promote chondrocyte autophagy
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Hypoxia-induced microRNA-146a represses Bcl-2 through Traf6/IRAK1 but not Smad4 to promote chondrocyte autophagy

  • Guanghui Chen , Xin Gao , Jing Wang , Cheng Yang , Yang Wang , Yonggang Liu , Weiwei Zou EMAIL logo and Tielong Liu EMAIL logo
Published/Copyright: November 15, 2016

Abstract

It has been shown that hypoxia stimulation promotes chondrocytes autophagy partly through HIF-1α, miR-146a and Bcl-2 progressively, and this mechanism represented the connection among hypoxia, miR-146a and autophagy, and provides a possible therapeutic strategy for osteoarthritis. However, the interaction between miR-146a and Bcl-2 is still unclear. Here in a hypoxic environment, we quantified the three reported miR-146a targets: two inflammation related targets Traf6, IRAK1; and the only reported target in chondrocytes Smad4. We confirmed the regulative function of miR-146a between hypoxia and these genes, and explored the Bcl-2 expression and autophagy level under extrinsic up-regulation of these three gene separately. All the three genes were down-regulated by hypoxia. Surprisingly, Traf6 and IRAK, but not the unique Smad4 in chondrocytes, were restored by antagomiR-146a. Both Ad-Traf6 and Ad-IRAK1 reinstated hypoxia or miR-146a repressed Bcl-2. However, Ad-Smad4 did not affect Bcl-2 in hypoxia or normoxia. The autophagy level showed a reverse variability compared to Bcl-2. Taken together, our results provided evidence that Smad4, the unique reported target for miR-146a in chondrocytes is unusually not involved in the chondrocytes autophagy, while the Traf6 and IRAK1 are the new targets for miR-146a in chondrocytes during autophagy.

Award Identifier / Grant number: 81372874

Funding statement: This work was supported by the National Natural Science Foundation of China (Grant 81372874).

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant 81372874).

  1. Conflict of interest statement: The authors indicate no potential conflicts of interest.

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Received: 2016-5-14
Accepted: 2016-10-4
Published Online: 2016-11-15
Published in Print: 2017-4-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

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