Research Papers:
microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1
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Abstract
Gang Liu1,*, Feng-Li Chen2,*, Feng Ji1, Hao-Dong Fei1,*, Yue Xie1 and Shou-Guo Wang1
1Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China
2Clinical Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China
*Co-first authors
Correspondence to:
Feng Ji, email: [email protected]
Shou-Guo Wang, email: [email protected]
Keywords: dexamethasone; osteoblasts; microRNA-19a; tuberous sclerosis complex 1 (TSC1); mTOR complex 1 (mTORC1)
Received: September 11, 2017 Accepted: December 08, 2017 Published: December 15, 2017
ABSTRACT
Activation of mTOR complex 1 (mTORC1) could protect human osteoblasts from dexamethasone. Tuberous sclerosis complex 1 (TSC1) is mTORC1 upstream inhibitory protein. We demonstrate here that microRNA-19a (“miR-19a”, -3p) targets the 3' untranslated regions of TSC1 mRNA. Expression of miR-19a downregulated TSC1 in OB-6 osteoblastic cells and primary human osteoblasts. miR-19a activated mTORC1 and protected human osteoblasts from dexamethasone. mTORC1 inhibition, by RAD001 or Raptor shRNA, almost completely abolished miR-19a-induced osteoblast cytoprotection against dexamethasone. Knockdown of TSC1 by targeted shRNA similarly induced mTORC1 activation and protected osteoblasts. Moreover, miR-19a activated mTORC1-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited dexamethasone-induced reactive oxygen species production in osteoblasts. Together, miR-19a protects human osteoblasts from dexamethasone possibly via targeting TSC1-mTORC1 signaling.
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