Magnesium promotes osteogenesis via increasing OPN expression and activating CaM/CaMKIV/CREB1 pathway

Area of Science:

• Biomaterials Science
• Orthopedic Research
• Cellular and Molecular Biology

Background:

• Magnesium (Mg) alloys are effective biodegradable implants for fracture repair.
• Magnesium ions (Mg2+) promote osteogenesis, the formation of new bone.

Purpose of the Study:

• Investigate the osteogenic properties of magnesium in vitro and in vivo.
• Identify the cellular and molecular mechanisms underlying magnesium-induced osteogenesis.

Main Methods:

• Cell proliferation assays (MC3T3, MG63 cells).
• Osteopontin (OPN) expression analysis.
• Protein-protein interaction (PPI) network analysis.
• Western blotting for p-CaMKIV/CaMKIV and p-CREB1/CREB.
• Dual-luciferase reporter gene assay.
• Gene silencing (sh-CaMKIV, sh-CREB1).
• In vivo studies with Mg screws and CaMKIV inhibitor (KN93).

Main Results:

• Mg2+ dose-dependently increased cell proliferation and OPN expression.
• Mg2+ treatment elevated p-CaMKIV and p-CREB1 levels.
• CREB1 directly binds to the OPN promoter, upregulating OPN transcription.
• Silencing CaMKIV or CREB1 reduced OPN and p-CREB1 expression.
• Inhibition of CaMKIV decreased mineralized deposit and OPN expression.
• In vivo, KN93 treatment led to bone cavities around Mg screws.

Conclusions:

• Magnesium's osteogenic effect is mediated by the CaM/CaMKIV/CREB1 signaling pathway.
• This pathway leads to the activation of OPN, promoting bone formation.
• Findings support Mg-based implants for enhanced fracture healing.