Osteopontin induces cyclo-oxygenase-2 expression in osteoclasts

Osteopontin (OPN) is a secreted phosphoprotein that is abundant in the bone matrix and plays an important role in bone homeostasis. Cortical bone in OPN^null mice has a heterogenous mineral density and reduced fracture toughness indicative of a defect in bone homeostasis. Osteoclasts binding to bone appears to be mediated by OPN at the surface of bone matrix interacting with the integrin αvß3 receptor that is abundantly expressed on osteoclasts. Activation of integrin αvß3 leads to cytoskeletal reorganization in the osteoclast that promotes binding and bone resorption. OPN also interacts with CD44 on the osteoclast surface which appears to promote osteoclast motility. Both integrin αvß3 and CD44 dependent signaling can induce cyclooxygenase-2 (COX-2) expression in non-skeletal cells. Our lab also recently found that OPN^null mice showed reduced COX-2 expression in fracture callus osteoclasts. Therefore, we wished to determine whether OPN could induce COX-2 expression in osteoclasts. Here, we show OPN induces COX-2 expression in osteoclasts through not only integrin αvβ3, but also the CD44 receptor. The results suggest that autocrine or paracrine signaling by osteoclasts may be mediated by COX-2.