Osteoactivin is a novel osteoclastic protein and plays a key role in osteoclast differentiation and activity

Abstract 

This study presents gene expression, protein expression, and in situ immunohistochemical evidence that osteoclasts express high levels of osteoactivin (OA), which had previously been reported to be an osteoblast-specific protein in bone. OA expression in osteoclasts was up-regulated upon receptor activator of NFκB ligand-induced differentiation. Suppression of functional activity of OA with neutralizing antibody reduced cell size, number of nuclei, fusion, and bone resorption activity of osteoclasts. OA was co-immunoprecipitated with integrin β₃ and β₁, indicating that OA co-localizes with integrin β₃ and/or β₁ in a hetero-polymeric complex in osteoclasts. These findings indicate that OA is a novel osteoclastic protein and plays a role in osteoclast differentiation and/or activity.

Abbreviations: OA, osteoactivin, Dchil, dendritic cell-associated, heparan sulfate proteoglycan-dependent integrin ligand, Gpnmb, glycoprotein non-metastatic melanomal protein B, MMP, matrix metalloproteinase, RGD, arginine-glycine-aspartic acid motif, BMP, bone morphogenetic protein, RANKL, receptor activator of NFκB ligand, DMEM, Dulbecco’s modified Eagle’s medium, α-MEM, minimum essential medium α, CM, conditioned medium, TRACP, tartrate-resistant acid phosphatase, RT-PCR, reverse transcriptase-polymerase chain reaction, C_T, cycle threshold

Keywords: Osteoactivin, Osteoclast, Bone resorption, Fusion, Spreading, Integrin