Gene expression during osteoclast-like cell formation induced by antifusion regulatory protein-1/CD98/4F2 monoclonal antibodies (MAbs): c-src is selectively induced by Anti-FRP-1 MAb

Human blood monocytes can differentiate into osteoclast-like cells when the y are cultured in the presence of anti-FRP-1, Messenger (mRNA) expression o f markers related to osteoclasts was analyzed during differentiation of ost eoclasts from monocytes, As markers related to osteoclasts, we selected cat hepsin-K, carbonic anhydrase (CA) II, vacuolar H+-ATPase (v-ATPase), vitron ectin receptor (VNR), tartrate-resistant acid phosphatase (TRAP), osteopont in (OPN), galectin-3, c-src, c-fos, and c-fms, The mRNAs other than c-src m RNA were expressed in freshly isolated monocytes or monocytes incubated wit h control antibody or anti-FRP-1 monoclonal antibody (MAb) for 14 days, Of these mRNAs, cathepsin-K, CA II, v-ATPase, VNR, TRAP, OPN, and c-fms mRNAs were expressed at higher levels in the osteoclast-like cells than those in monocytes cultured with control antibody, On the other hand, galectin-3 mRN A was expressed at lower levels in the osteoclast-like cells, and there was no significant difference in c-fos mRNA expression between the monocytes c ultured with control antibody and anti-FRP-1 MAb. c-src mRNA could not be d etected in monocytes freshly isolated or incubated with control antibody. S urprisingly, expression of c-src mRNA was induced in monocytes by anti-FRP- 1 MAb and was detectable as early as 3 h after anti-FRP-1 MAb treatment, in dicating that c-src is selectively induced ba anti-FRP-1 MAb treatment. Fur thermore, the osteoclast-like cells expressed calcitonin receptor. Receptor activator of NF-KB (RANK) mRNA was detectable in freshly isolated monocyte s or monocytes cultured with control antibody or anti-FRP-1 MAbs. Maximal e xpression of RANK was observed in osteoclast-like cells. On the other hand, no receptor activator of NF-kappa B ligand (RANKL) mRNA was detectable in any of the samples, suggesting that anti-FRP-1 mAb can induce osteoclast-li ke cells from blood monocytes without RANKL. (C) 1999 by Elsevier Science I nc. All rights reserved.