Blocking CCN2 preferentially inhibits osteoclastogenesis induced by repetitive high force bone loading

Area of Science:

• Bone Biology
• Skeletal Physiology
• Connective Tissue Growth Factor (CCN2) Biology

Background:

• Overuse-induced bone loss is a concern in repetitive mechanical loading.
• Connective Tissue Growth Factor (CCN2) signaling is implicated in bone remodeling and fibrosis.
• A monoclonal antibody (FG-3019) targeting CCN2 shows potential for treating fibrosis.

Purpose of the Study:

• To investigate if blocking CCN2 signaling with FG-3019 can mitigate early bone catabolism induced by a high repetition high force (HRHF) task.
• To assess the effects of CCN2 blockade on trabecular bone volume and resorption markers during HRHF loading.

Main Methods:

• Female Sprague-Dawley rats were trained for a HRHF lever-pulling task for 3 weeks.
• Treatment groups included HRHF untreated, HRHF + FG-3019 antibody, and HRHF + IgG control.
• Bone parameters and serum C-terminal telopeptide type 1 (CTX-1) were analyzed.

Main Results:

• HRHF loading increased bone formation but decreased trabecular bone volume and increased osteoclast numbers and serum CTX-1 in untreated and IgG groups.
• FG-3019 treatment maintained higher trabecular bone volume and reduced osteoclast numbers and serum CTX-1 compared to HRHF untreated/IgG groups.
• Bone formation remained elevated in the FG-3019 group, similar to other HRHF groups.

Conclusions:

• HRHF loading stimulates bone formation but also induces bone catabolism.
• Blocking CCN2 signaling with FG-3019 effectively dampens HRHF-induced trabecular bone loss by reducing osteoclast activity.
• CCN2 antagonism represents a potential therapeutic strategy against overuse-induced bone catabolism.