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Sinomenine increases osteogenesis in mice with ovariectomy-induced bone loss by modulating autophagy
Hai-Xiang Xiao1,2,3, Lei Yu3, Yu Xia3
1Department of Orthopedics, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Centre of Soochow University, Suzhou 215006, Jiangsu Province, China.
Background:
A decreased autophagic capacity of bone marrow mesenchymal stromal cells (BMSCs) has been suggested to be an important cause of decreased osteogenic differentiation. A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.
Aim:
To explore the effects of sinomenine (SIN) on the osteogenic differentiation of BMSCs and the underlying mechanisms.
Methods:
For in vitro experiments, BMSCs were extracted from sham-treated mice and ovariectomized mice, and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concentrations of SIN and the autophagy inhibitor 3-methyladenine. In vivo, the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.
Results:
SIN reduced the levels of AKT and mammalian target of the rapamycin (mTOR) phosphorylation in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway, inhibited mTOR activity, and increased autophagy ability of BMSCs, thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.
Conclusion:
The Chinese medicine SIN has potential for the treatment of various types of osteoporosis, bone homeostasis disorders, and autophagy-related diseases.
