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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

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Source Normalized Impact per Paper (SNIP) 2018: 0.820

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Volume 398, Issue 4


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

Guanghui Chen / Xin Gao
  • The Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jing Wang
  • The Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Cheng Yang
  • The Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yang Wang
  • The Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
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  • De Gruyter OnlineGoogle Scholar
/ Yonggang Liu
  • The Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
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/ Weiwei Zou
  • Corresponding author
  • The Department of Medical Imaging Diagnosis, Changzheng Hospital, Second Military Medical University, Shanghai, China
  • Email
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/ Tielong Liu
  • Corresponding author
  • The Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
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Published Online: 2016-11-15 | DOI: https://doi.org/10.1515/hsz-2016-0211


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.

Keywords: autophagy; chondrocytes; IRAK1; miR-146a; Smad4; Traf6


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About the article

aGuanghui Chen, Xin Gao and Jing Wang: These authors contributed equally to this work.

Received: 2016-05-14

Accepted: 2016-10-04

Published Online: 2016-11-15

Published in Print: 2017-04-01

Funding Source: National Natural Science Foundation of China

Award identifier / Grant number: 81372874

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

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

Citation Information: Biological Chemistry, Volume 398, Issue 4, Pages 499–507, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2016-0211.

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