CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

Area of Science:

• Biomedical Engineering
• Orthodontics
• Cell Biology

Background:

• Orthodontic treatment aims to accelerate tooth movement, but osteoclast-mediated bone resorption is a limiting factor.
• Mechanoreceptors, particularly adhesion G protein-coupled receptors (aGPCRs) on macrophages, are involved in force sensing, but their role in osteoclast differentiation is unclear.

Purpose of the Study:

• To investigate the role of CD97, a mechanosensitive aGPCR, in regulating osteoclast differentiation under compressive force during orthodontic tooth movement.
• To elucidate the signaling pathway mediating CD97's effects on osteoclast differentiation.

Main Methods:

• Single-cell analysis to identify CD97 expression in macrophages.
• Experimental manipulation of CD97 expression (upregulation/knockdown) under compression.
• RNA sequencing to analyze signaling pathways.
• Pharmacological inhibition of the Rap1a pathway using GGTI298.

Main Results:

• CD97 is expressed in macrophages and its expression is upregulated by compression.
• Upregulated CD97 inhibits osteoclast differentiation, while CD97 knockdown partially rescues this inhibition.
• The Rap1a/ERK signaling pathway mediates CD97's inhibitory effect on osteoclast differentiation.
• Inhibition of Rap1a with GGTI298 increases osteoclast activity and accelerates tooth movement.

Conclusions:

• CD97 acts as a mechanosensitive receptor that suppresses osteoclast differentiation under orthodontic compressive force.
• The CD97-mediated suppression of osteoclastogenesis occurs via the Rap1a/ERK signaling pathway.
• Targeting the Rap1a pathway offers a potential strategy for accelerating orthodontic tooth movement.