Curcumin Alleviates the Osteogenesis Inhibition and the Aging Process in BMSCs Induced by Iron Overload Through...

Area of Science:

• Biomedical Science
• Cell Biology
• Osteoporosis Research

Background:

• Dysregulated bone marrow mesenchymal stem cells (BMSCs) drive osteoporosis.
• Ferroptosis is increasingly linked to osteoporosis progression.
• Curcumin shows promise for bone disorders, but its mechanism via ferroptosis is unclear.

Purpose of the Study:

• To investigate if curcumin alleviates iron overload-induced BMSC dysfunction by targeting ferroptosis.
• To elucidate curcumin's molecular mechanisms in promoting osteogenic differentiation and mitigating senescence.
• To explore the role of the Nrf2/GPX4 pathway in curcumin's effects.

Main Methods:

• Established in vitro and in vivo models of iron overload-induced osteoporosis.
• Administered curcumin and assessed outcomes using micro-CT, RNA-seq, RT-qPCR, Western blot, and TEM.
• Utilized Nrf2 siRNA and ML385 inhibitor to probe the Nrf2/GPX4 pathway.

Main Results:

• Curcumin treatment improved bone microstructure and mechanical properties in vivo.
• In vitro, curcumin reduced ferroptosis by upregulating Nrf2 and GPX4 expression.
• Curcumin delayed BMSC senescence and promoted osteogenic differentiation.

Conclusions:

• Curcumin ameliorates iron overload-induced osteoporosis by targeting ferroptosis via the Nrf2/GPX4 axis.
• This study identifies the Nrf2/GPX4 pathway as a key therapeutic target for osteoporosis.
• Findings support curcumin as a potential therapeutic agent for age-related and postmenopausal osteoporosis.