Regulation of osteoclastogenesis by moesin. Myeloid progenitors stimulated by RANKL and M-CSF differentiate into β3-integrin–expressing osteoclasts. When these osteoclasts attach to bone, β3-integrin–RhoA–SLK signaling activates moesin. Moesin anchors actin filaments to the plasma membrane, stabilizing the sealing zone and ruffled border needed for controlled bone resorption. Loss of moesin or its inhibition by inflammatory cues weakens this anchorage, promotes TNT formation (not depicted), drives excessive fusion of osteoclasts, and results in increased bone resorption.