Open AccessSuppression of AMP‐activated protein kinase reverses osteoprotegerin‐induced inhibition of osteoclast differentiation by reducing autophagy
Author(s) -
Tong Xishuai,
Zhang Chuang,
Wang Dong,
Song Ruilong,
Ma Yonggang,
Cao Ying,
Zhao Hongyan,
Bian Jianchun,
Gu Jianhong,
Liu Zongping
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12714
Subject(s) - ampk , autophagy , protein kinase a , chemistry , microbiology and biotechnology , osteoclast , pi3k/akt/mtor pathway , osteoprotegerin , activator (genetics) , amp activated protein kinase , signal transduction , mechanistic target of rapamycin , kinase , biology , biochemistry , in vitro , apoptosis , receptor
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.