Fabp5 Is the Key Regulator Mediating γ-CEHC Differentiation in Osteoblasts and Osteoclasts

Area of Science:

• Biochemistry
• Molecular Biology
• Bone Biology

Background:

• Osteoporosis is linked to oxidative stress and inflammation.
• Vitamin E metabolite γ-CEHC possesses antioxidant and anti-inflammatory properties.
• The molecular targets of γ-CEHC in bone metabolism are largely unknown.

Purpose of the Study:

• To identify protein targets of γ-CEHC.
• To elucidate the role of γ-CEHC in regulating bone metabolism.
• To investigate γ-CEHC as a therapeutic agent for osteoporosis.

Main Methods:

• Ovariectomized (OVX) mouse model and in vitro assays.
• Isothermal thermal proteome profiling (TPP) to identify protein targets.
• Cellular thermal shift assays (CETSA) and Surface Plasmon Resonance (SPR) for binding confirmation.

Main Results:

• γ-CEHC inhibits osteoclast differentiation and enhances osteoblast differentiation in OVX mice.
• Fatty acid-binding protein 5 (Fabp5) identified as a core target of γ-CEHC.
• γ-CEHC suppresses M1 macrophage activation, promotes M2 polarization, and reduces reactive oxygen species (ROS).

Conclusions:

• γ-CEHC acts as a selective ligand for Fabp5, offering a novel therapeutic approach for osteoporosis.
• γ-CEHC improves bone metabolism by modulating macrophage polarization and reducing oxidative stress.
• This study provides a mechanistic basis for targeting Fabp5 in osteoporosis treatment.