Suppression of AMP‚Äêactivated protein kinase reverses osteoprotegerin‚Äêinduced inhibition of osteoclast differentiation by reducing autophagy
Authors: Ruilong Song
Xishuai Tong
Hongyan Zhao
Jianhong Gu
Dong Wang
Zongping Liu
Yonggang Ma
Jianchun Bian
Chuang Zhang
Ying Cao
Journal: Cell Proliferation (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AMP-activated protein kinase (AMPK); mammalian target of rapamycin (mTOR); osteoclasts; osteoprotegerin; ribosomal protein S6 kinase beta-1 (p70S6K).
Affiliations: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China., Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, China., Jiangsu Key Laboratory of Zoonosis, Yangzhou, Jiangsu, China., Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, China., Key Laboratory of Neurodegeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neurodegeneration, Nantong University, Nantong, Jiangsu, China.

Abstract:  Objectives: Osteoclasts (OC) are unique terminally differentiated cells whose primary function is bone resorption. We previously showed that osteoprotegerin (OPG) inhibits OC differentiation in vitro by enhancing autophagy via the adenosine monophosphate-activated protein kinase (AMPK)/mTOR/p70S6K signalling pathway in vitro. Here, we aimed to elucidate the mechanism of AMPK mediated autophagy to regulate OPG-mediated inhibition of OC differentiation and identify potential therapeutic targets associated with bone loss. Materials and methods: We used the AMPK activator AICAR to determine the relationship between AMPK activation and OC differentiation, and studied the role of AMPK-mediated autophagy in OPG-mediated inhibition of OC differentiation by using autophagy inhibitors or AMPK knockdown. Results: AMP-activated protein kinase activation caused LC3II accumulation and weakened OC differentiation activity. In contrast, inactivation of autophagy by 3-methyladenine or Bafilomycin A1 could attenuate OPG-mediated inhibition of OC differentiation via the AMPK/mTOR/p70S6K signalling pathway. Furthermore, the AMPK inhibitor compound C and knockdown of AMPK impaired OPG-mediated inhibition of OC differentiation by inducing autophagy. Conclusions: These results demonstrated that the AMPK signalling pathway functions as a critical regulator in the OPG-mediated inhibition of OC differentiation, by inducing autophagy. Our results provide a basis for future bone-related studies on the AMPK signalling pathway. 

Retracted: No

PubPeer comments:
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