Complement-dependent stimulation of prostaglandin synthesis and bone resorption.

Area of Science:

• Immunology
• Biochemistry
• Skeletal Biology

Background:

• The complement system is a crucial part of innate immunity.
• Prostaglandins are signaling molecules involved in various physiological processes, including bone metabolism.
• The role of specific complement components in bone resorption mediated by prostaglandins is not fully understood.

Purpose of the Study:

• To investigate the role of complement-sufficient heterologous serum in inducing prostaglandin synthesis and bone resorption in fetal rat long bones.
• To determine the specific contribution of the sixth component of complement (C6) to this process.
• To elucidate the involvement of prostaglandin E in complement-mediated bone resorption.

Main Methods:

• Cultures of fetal rat long bones were incubated with different types of rabbit serum (unheated, heated, C6-deficient, C6-reconstituted).
• Bone resorption was quantified.
• Prostaglandin E concentrations in culture media were measured using radioimmunoassay.
• The effect of indomethacin, a prostaglandin synthesis inhibitor, was assessed.

Main Results:

• Complement-sufficient heterologous serum induced significant prostaglandin synthesis and bone resorption.
• Unheated normal rabbit serum showed enhanced resorptive activity compared to heated serum or C6-deficient serum.
• Addition of purified C6 restored resorptive activity in C6-deficient serum.
• Prostaglandin E levels increased in media incubated with complement-sufficient serum.
• Indomethacin inhibited both serum-induced bone resorption and prostaglandin E production.

Conclusions:

• Complement activation in serum can stimulate prostaglandin synthesis, leading to bone resorption in fetal rat long bones.
• The sixth component of complement (C6) plays a role in this process.
• Prostaglandin E is a key mediator of complement-induced bone resorption.
• Inhibition of prostaglandin synthesis effectively blocks complement-mediated bone resorption.