Ameloblastin modulates osteoclastogenesis through the integrin/ERK pathway

► In transgenic mice the matrix adhesion protein ameloblastin (AMBN) caused root cementum resorption, delamination, and reduced alveolar bone thickness. ► AMBN modulated osteoclast differentiation from bone marrow monocytes, and dramatically increased osteoclast numbers and resorption pits. ► AMBN more than doubled BMMC adhesion, accelerated cell spreading, and promoted podosome belt and actin ring formation. ► ERK1/2 phosphorylation were elevated and block of integrin/ERK pathways alleviated the effects of AMBN on osteoclast differentiation. ► AMBN increased mineralized tissue resorption by regulating adhesion, cytoskeleton polymerization, and enhancing osteoclastogenesis.