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Sinomenine increases osteogenesis in mice with ovariectomy-induced bone loss by modulating autophagy

sarah Jonas

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.

Key Words: Sinomenine, Osteogenesis, Autophagy, Ovariectomy, Osteoporosis

Core Tip: Sinomenine (SIN) reduces the levels of AKT and mammalian target of the rapamycin (mTOR) phosphorylation in the phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway, inhibits mTOR activity, and increases autophagy of bone marrow mesenchymal stromal cells (BMSCs), thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice when used in vivo, thus providing support for the use of the traditional Chinese medicine SIN in the treatment of various types of osteoporosis, imbalances in bone homeostasis, and autophagy-related diseases.