Dexamethasone-induced apoptosis of osteocytic and osteoblastic cells is mediated by TAK1 activation

Biochemical and Biophysical Research Communications
Heyuan DingYiming Li

Abstract

Increased apoptosis of osteoblasts and osteocytes is the main mechanism of glucocorticoid (GC)-induced osteonecrosis. In the current study, we investigated whether dexamethasone (Dex)-induced osteoblastic and osteocytic cell apoptosis is mediated through activation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), and whether TAK1 inhibition could promote survival opposing the deleterious effects of Dex. We found that TAK1 was activated by Dex in both osteocytic MLO-Y4 and osteoblastic OB-6 cells, which was prevented by two known anti-oxidants N-acetylcysteine (NAC) and ebselen. TAK1 inhibitors, including LYTAK1 and 5Z-7-oxozeaenol (57-OZ), inhibited Dex-induced apoptosis of MLO-Y4 and OB-6 cells. Meanwhile shRNA-mediated knockdown of TAK1 also suppressed Dex-induced damages to MLO-Y4 and OB-6 cells. On the other hand, exogenously over-expressing TAK1 enhanced Dex-induced MLO-Y4 and OB-6 cell apoptosis. At the molecular level, we found that TAK1 mediated Dex-induced pro-apoptotic Pyk2-JNK activation. Inhibition or silencing of TAK1 almost abolished Pyk2-JNK phosphorylations by Dex in MLO-Y4 and OB-6 cells. TAK1 over-expression, on the other hand, increased Dex's activity on Pyk2-JNK phosphorylations in above ce...Continue Reading

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Citations

Dec 2, 2015·Biochemical and Biophysical Research Communications·Xi FengXiujuan Wang
Oct 31, 2015·Biochemical and Biophysical Research Communications·Haibin Jiang, Zhiyuan Zeng
Sep 11, 2016·Biochemical and Biophysical Research Communications·Song-Tao LiXiao-Zhong Zhou
Jun 3, 2017·Oncotarget·Hao-Dong FeiFeng Ji
Dec 30, 2017·Oncotarget·Dawei XuZhiming Cui
Mar 8, 2018·International Journal of Molecular Medicine·Ding ZhouChang-Qing Zhang
Jul 28, 2020·International Journal of Molecular Sciences·Nina FrieseAndrea Hoffmann
Mar 31, 2019·Journal of Nephrology·Claudio Ponticelli, Richard J Glassock
Nov 27, 2019·Cell Death & Disease·Jinqian LiangMing-Sheng Tan
Jul 5, 2017·Experimental and Therapeutic Medicine·Xuan'An LiGuang-Hua Lei
Oct 22, 2020·Acta Biochimica Et Biophysica Sinica·Huaqiang TaoDechun Geng
Jun 28, 2019·Biochemical and Biophysical Research Communications·Cong-Ya ZhuXiao-Zhong Zhou
Aug 5, 2019·Biochemical and Biophysical Research Communications·Hongxiang HongZhiming Cui
May 20, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tian QingShen Zhongyang

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