JAK inhibition ameliorates bone destructions by simultaneously targeting mature osteoclasts and their precursor stages

Inflammatory bone destruction was induced by locally injecting lipopolysaccharides into fluorescent reporter mice of mature osteoclasts or their precursors. These mice were treated with a JAK inhibitor, ABT-317, which selectively inhibits the activation of JAK1, and intravital imaging with multiphoton microscopy was conducted. We also investigated the molecular mechanism of the effects of the JAK inhibitor on osteoclasts by exhaustive RNA sequence analysis. Overall design: To reveal the molecular mechanism that JAK inhibitor prevented the migration of osteoclast precursors to the bone surface, CX3CR1-EGFP+ cells were isolated from calvaria in LPS-induced inflammatory bone destruction model mice which were treated with JAK inhibitor or vehicle, and RNA sequence analysis was performed.