Reduced bone loss in a murine model of postmenopausal osteoporosis lacking complement component 3

Area of Science:

• Osteoimmunology
• Skeletal biology
• Immunology

Background:

• Osteoimmunology investigates the interplay between skeletal and immune systems.
• Complement signaling impacts osteoblast and osteoclast differentiation, crucial for bone homeostasis.
• The in vivo effect of complement on bone homeostasis remained unclear.

Purpose of the Study:

• To determine the in vivo effect of complement component 3 (C3) deficiency on bone loss in a postmenopausal osteoporosis model.
• To test the hypothesis that C3 deficiency protects against ovariectomy-induced bone loss.

Main Methods:

• Ovariectomy (OVX) or sham surgery was performed on wild-type (WT) and C3-deficient (C3-/-) mice.
• Microcomputed tomography (MicroCT) analyzed bone structure (trabecular bone volume fraction).
• Mechanical testing assessed femoral neck stiffness.
• Osteoid content and mineral apposition rates were measured in lumbar vertebrae.

Main Results:

• OVX C3-/- mice exhibited significantly reduced bone loss compared to OVX WT mice at multiple skeletal sites.
• Femoral neck stiffness was significantly increased in OVX C3-/- mice.
• Lumbar vertebrae showed increased osteoid content and mineral apposition rates in OVX C3-/- mice.

Conclusions:

• C3 deficiency significantly reduces bone loss following ovariectomy.
• Absence of C3 may improve the mechanical properties of bone, potentially enhancing fracture resistance.
• These findings highlight C3 as a potential therapeutic target for osteoporosis.