Liquiritigenin promotes osteogenic differentiation and prevents bone loss via inducing auto-lysosomal degradation and inhibiting apoptosis

作者全名："Qiu, Yu; Zhao, Yueyang; Long, Zhimin; Song, Aijia; Huang, Peng; Wang, Kejian; Xu, Ling; Molloy, David Paul; He, Guiqiong"

作者地址："[Qiu, Yu; Xu, Ling] Chongqing Med Univ, Coll Stomatol, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Qiu, Yu; Zhao, Yueyang; Long, Zhimin; Wang, Kejian; He, Guiqiong] Chongqing Med Univ, Chongqing Key Lab Neurobiol, Chongqing 400016, Peoples R China; [Zhao, Yueyang; Long, Zhimin; Wang, Kejian; He, Guiqiong] Chongqing Med Univ, Dept Anat, Chongqing 400016, Peoples R China; [Song, Aijia; Huang, Peng] Chongqing Med Univ, Inst Life Sci, Lab Med Expt Technol, Chongqing 400016, Peoples R China; [Molloy, David Paul] Chongqing Med Univ, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [He, Guiqiong] Chongqing Med Univ, Chongqing Key Lab Neurobiol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Xu, Ling] Chongqing Med Univ, Stomatol Hosp, Dept Prosthodont, 426 Songshibei Rd, Chongqing 401147, Peoples R China; [Molloy, David Paul] Chongqing Med Univ, Dept Biochem & Mol Biol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："He, GQ (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Neurobiol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Xu, L (通讯作者)，Chongqing Med Univ, Stomatol Hosp, Dept Prosthodont, 426 Songshibei Rd, Chongqing 401147, Peoples R China.; Molloy, DP (通讯作者)，Chongqing Med Univ, Dept Biochem & Mol Biol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000983990100001

JCR分区：Q1

影响因子：6.8

年份：2023

卷号：10

期号：1

开始页：284

结束页：300

文献类型：Article

关键词：Auto-lysosomal; Liquiritigenin; differentiation; degradation; Osteogenic

摘要："Osteoporosis (OP) is a debilitating skeletal abnormality involving bone remodeling and bone cell homeostasis characterized by decreased bone strength and high fracture risk. A novel therapeutic intervention for OP by manipulating cellular autophagy-apoptosis processes to promote skeletal homeostasis is presented. Protective effects of the naturally occurring plant extract Liquiritigenin (LG) were demonstrated in an ovariectomy (OVX)-OP mouse model and preosteoblast MC3T3-E1 cells. Micro-CT and histological staining assessments of skeletal phenotype were applied alongside detection of autophagy activity in osteocytes and MC3T3 E1 cells by transmission electron microscopy (TEM). The effects of LG on chloroquine (CQ)- and the apoptosis-inducing TS-treated osteogenic differentiations and status of lysosomes within MC3T3-E1 cells were analyzed by Neutral red, Alizarin red S and alkaline phosphatase (ALP) staining and Western blot assays. Treatment with LG prevented bone loss, increased osteogenic differentiation in vivo and in vitro, and inhibited osteoclast formation to some extent. TEM analyses revealed that LG can improve auto-lysosomal degradation within osteocytes from OVX mice and MC3T3-E1 cells. The abnormal status of lysosomes associated with CQ and TS treatments was notably alleviated by LG which also reduced levels of apoptosis-induced inhibition of osteogenic differentiation and averted abnormal osteogenic differentiation as a consequence of a blockage in autolysosome degradation. Overall, LG stimulates bone growth in OVX mice through increased osteogenic differentiation and regulation of autophagyapoptosis mechanisms, presenting an auspicious natural therapy for OP. 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons."

基金机构："National Natural Science Foundation of China [81671257, 81371221, CXQTP19019019034]; Innovation Research Group at Institutions of Higher Education in Chongqing, China; Program for Innovation Team Building at Institutions of Higher Education in Chongqing; [31600825]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (No. 81671257, 81371221, 31600825) 81671257, 81371221, 31600825) Innovation Research Group at Institutions of Higher Education in Chongqing, China (No. CXQTP19019019034) Program for Innovation Team Building at Institutions of Higher Education in Chongqing in 2016."