Hyperocclusion up-regulates CCL3 expression in CCL2- and CCR2-deficient mice

Area of Science:

• Oral biology and pathology
• Immunology
• Skeletal biology

Background:

• Excessive mechanical stress (MS) in hyperocclusion causes alveolar bone destruction, termed occlusal traumatism.
• MS induces C-C chemokine ligand 2 (CCL2) expression in periodontal ligament (PDL) tissues, driving MS-dependent osteoclastogenesis via C-C chemokine receptor 2 (CCR2).

Purpose of the Study:

• To investigate the role of the CCL2/CCR2 signaling pathway in mechanical stress-induced osteoclastogenesis and alveolar bone destruction.
• To determine if ablating the CCL2/CCR2 pathway alleviates occlusal traumatism by suppressing chemokine-driven osteoclastogenesis.

Main Methods:

• Utilized in vivo and in vitro hyperocclusion models in wild-type, CCL2-deficient (CCL2((-/-))), and CCR2-deficient (CCR2((-/-))) mice.
• Assessed chemokine expression (CCL3) in PDL cells and quantified osteoclastogenesis (TRAP-positive cells) in alveolar bone under normal and MS conditions.

Main Results:

• CCL2((-/-)) and CCR2((-/-))) mice exhibited up-regulated CCL3 expression and increased TRAP-positive cells in PDL and alveolar bone, even without MS.
• Hyperocclusion loading significantly increased CCL3 expression and osteoclastogenesis in CCL2((-/-)) and CCR2((-/-))) mice after 4 and 7 days.
• These findings suggest compensatory CCL3 upregulation and osteoclastogenesis to counteract the deficient CCL2/CCR2 signaling.

Conclusions:

• Ablation of the CCL2/CCR2 pathway does not prevent MS-induced osteoclastogenesis but leads to compensatory CCL3 upregulation.
• Co-expression of CCL3 with CCL2 may synergistically enhance MS-dependent alveolar bone destruction in occlusal traumatism.
• Targeting both CCL2/CCR2 and CCL3 pathways may be necessary to effectively treat occlusal traumatism.