Sweroside-mediated mTORC1 hyperactivation in bone marrow mesenchymal stem cells promotes osteogenic differentiation

Area of Science:

• Pharmacology
• Biomedical Engineering
• Cell Biology

Background:

• Osteoporosis (OP) is a significant skeletal disorder characterized by decreased bone mass and increased fracture risk.
• Postmenopausal osteoporosis is a major health concern, necessitating novel therapeutic strategies.
• Sweroside (SOS), a natural compound, has shown potential therapeutic benefits, but its molecular mechanisms in OP remain to be fully elucidated.

Purpose of the Study:

• To investigate the preventive effects of sweroside (SOS) on osteoporosis (OP) in an ovariectomized (OVX) mouse model.
• To elucidate the molecular mechanisms underlying SOS's action on bone metabolism and osteoblast differentiation.
• To explore the role of the mTORC1 signaling pathway in SOS-mediated OP prevention.

Main Methods:

• Ovariectomized (OVX) mice were treated with SOS (120 mg/kg/day) for 3 months to assess in vivo effects.
• Bone morphology was evaluated using hematoxylin and eosin (HE) staining and micro-computed tomography (CT).
• In vitro studies involved treating bone marrow mesenchymal stem cells (BMSCs) with SOS and rapamycin to analyze osteogenic differentiation and signaling pathway activation via Western blotting and RT-PCR.

Main Results:

• In vivo studies demonstrated that SOS treatment alleviated OP, improving bone mineral density, trabecular thickness, and trabecular number in OVX mice.
• SOS significantly promoted osteoblast differentiation and the expression of key osteogenic markers (RUNX2, OSX, OCN) in BMSCs.
• SOS activated the mTORC1/PS6 signaling pathway, which was essential for its osteogenic effects, as rapamycin treatment reversed these outcomes.

Conclusions:

• Sweroside (SOS) effectively prevents osteoporosis by promoting the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts.
• The mechanism involves the upregulation of the mTORC1/PS6 signaling pathway, leading to increased expression of osteogenic markers.
• SOS represents a promising therapeutic agent for managing and preventing osteoporosis.