Bcl6 inhibits osteoclastogenesis by upregulating STAT1 phosphorylation.

BACKGROUND

The rate of orthodontic tooth movement (OTM) directly influences the duration of orthodontic treatment. OTM relies on the bone modeling under mechanical stress, wherein osteoclasts mediate bone resorption. Bcl6 and STAT1 serve as critical regulatory factors in the osteoclast differentiation pathway. This study aims to elucidate how Bcl6 and STAT1 interact to regulate osteoclast differentiation.

MATERIALS AND

RESULTS

RAW264.7 (mouse monocyte macrophages) were differentiated into osteoclasts using Receptor Activator of Nuclear Factor-κB Ligand (RANKL) and Macrophage colony-stimulating factor (M-CSF) induction. During osteoclast differentiation, RAW264.7 were treated with Fludarabine (a STAT1 inhibitor) or transfected with Bcl6 overexpression plasmids. Osteoclast differentiation, STAT1 expression, and phosphorylation levels were evaluated by TRAP staining, RT-qPCR, and Western blot analysis. Fludarabine promotes STAT1 phosphorylation, resulting in suppression of RAW264.7 osteoclast differentiation. Similarly, overexpression of Bcl6 enhances STAT1 phosphorylation and inhibits osteoclast differentiation in RAW264.7. The anti-osteoclastogenic effect induced by Bcl6 overexpression is further augmented by Fludarabine treatment.

CONCLUSION

Osteoclast differentiation of RAW264.7 cells induced by RANKL and M-CSF is suppressed through Bcl6-mediated STAT1 phosphorylation.