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

  • World J Stem Cells. 2024 May 26;16(5):486-498. doi: 10.4252/wjsc.v16.i5.486.
Hai-Xiang Xiao  1  2  3 ,  Lei Yu  3 ,  Yu Xia  3 ,  Kai Chen  4 ,  Wen-Ming Li  3 ,  Gao-Ran Ge  3 ,  Wei Zhang  3 ,  Qing Zhang  5 ,  Hong-Tao Zhang  6 ,  De-Chun Geng  7
Affiliations
  • 1. Department of Orthopedics, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Centre of Soochow University, Suzhou 215006, Jiangsu Province, China.
  • 2. Department of Orthopedics, Jingjiang People's Hospital Affiliated to Yangzhou University, Jingjiang 214500, Jiangsu Province, China.
  • 3. Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
  • 4. Department of Orthopedics, Hai'an People's Hospital, Hai'an 226600, Jiangsu Province, China.
  • 5. Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an Second People's Hospital, Xuzhou 223002, Jiangsu Province, China.
  • 6. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
  • 7. Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. [email protected].
PMID: 38817333 DOI: 10.4252/wjsc.v16.i5.486
Abstract

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.

Keywords
Autophagy; Osteogenesis; Osteoporosis; Ovariectomy; Sinomenine.
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