Yougui Pills Alleviate Osteoporosis by Inhibiting Mesenchymal Stem Cell ROS Accumulation via the Nrf2/HO-1 Pathway

Area of Science:

• Biomedical Science
• Traditional Chinese Medicine
• Cell Biology

Background:

• Osteoporosis (OP) is a skeletal disorder marked by bone loss and microarchitectural deterioration.
• Oxidative stress-induced mesenchymal stem cell (MSC) dysfunction is a key factor in osteoporosis pathogenesis.
• Yougui Pills (YGPs) are used clinically for OP, but their precise mechanisms are not fully understood.

Purpose of the Study:

• To investigate the bone-protective effects of YGPs in osteoporosis.
• To explore the underlying mechanisms, focusing on oxidative stress and the Nrf2/HO-1 pathway in MSCs.

Main Methods:

• In vivo studies using an ovariectomy-induced osteoporosis mouse model.
• In vitro experiments inducing oxidative stress in MSCs with hydrogen peroxide (H₂O₂).
• Micro-CT, histological assays, transcriptomic analysis, network pharmacology, and gene silencing (siRNA).

Main Results:

• YGPs improved bone mineral density and trabecular microstructure in OVX mice.
• YGPs reduced oxidative stress, apoptosis, and enhanced proliferation, migration, and osteogenic differentiation of MSCs.
• YGPs activated the Nrf2/HO-1 signaling pathway, crucial for their protective effects.

Conclusions:

• YGPs effectively mitigate osteoporosis by protecting MSCs from oxidative stress.
• The Nrf2/HO-1 pathway is a critical mediator of YGPs' anti-osteoporotic effects.
• YGPs show promise as a therapeutic agent for osteoporosis management.