OSTEOCLASTOGENESIS INHIBITORY FACTOR (OCIF) DIRECTLY INHIBITS BONE-RESORBING ACTIVITY OF ISOLATED MATURE OSTEOCLASTS

Osteoclastogenesis inhibitory factor (OCIF) was previously reported to specifically inhibit osteoclast development by interrupting the actio n of osteoclast differentiation factor (ODF), which is expressed in st romal cells and plays an important role in osteoclastogenesis. Here we report the direct action of OCIF on isolated rabbit mature osteoclast s to inhibit their functional bone-resorbing activity. The cell popula tion employed in this study consisted of mature osteoclasts with more than 95% of purity. The inhibition by OCIF was dose dependent and obse rved as early as 6 h after the OCIF addition. An OCIF-binding protein of 140 kDa was detected on the plasma membrane of osteoclasts. ODF wit h a Mr of 40 kDa was recently isolated as a ligand for OCIF and shows to be identical to TRANCE/RANKL. However, ODF was not detected in oste oclasts. OCIF did not have any impact on the mRNA levels of cathepsin K/OC2 and carbonic anhydrase II responsible for degradation of organic and inorganic bone matrices, respectively, or on osteoclast apoptosis . However, OCIF reduced or disrupted the formation of F-actin ring in isolated osteoclasts, the cytoskeletal structure of which is correlate d with bone resorption. These findings demonstrate that OCIF directly inhibits osteoclast function through an ODF-independent mechanism besi des blocking the generation of osteoclasts. (C) 1998 Academic Press.