In vitro anti-osteoclastogenic activity of p38 inhibitor doramapimod via inhibiting migration of pre-osteoclasts and NFATc1 activity.

The mitogen activated protein kinase p38 plays a role in the receptor activator of NF-ĸB ligand (RANKL)-induced osteoclast differentiation. In this study, we investigated the effect of p38 inhibitor doramapimod on the osteoclast differentiation. Doramapimod significantly inhibited the osteoclastogenesis of bone marrow macrophages (BMMs) via attenuating the activation of p38 induced by M-CSF and RANKL. Importantly, doramapimod blocked the migration and fusion in pre-osteoclasts via the down-regulating NFATc1. The inhibitory effect of doramapimod on the migration/fusion of pre-osteoclasts via inhibiting NFATc1 activity were confirmed by measuring NFATc1 luciferase activity and evaluating the mRNA expression of NFATc1-responsive genes related to the osteoclastic migration/fusion. These results suggested anti-osteoclastogenic activity of doramapimod via inhibiting migration/fusion of pre-osteoclasts and NFATc1 activity.