Suppression of FRP-1/CD98-mediated multinucleated giant cell and osteoclast formation by an anti-FRP-1/CD98 mAb, HBJ 127, that inhibits c-src expression

When anti-CD98 mAb 6-1-13, 4-5-1, or 38-2-2 was added to the culture, fluid s of monocytes, extensive cell aggregation and polykaryocyte formation were induced. These multinucleated giant cells were tartrate-resistant acid pho sphatase (TRAP) positive On the other hand, when monocytes were incubated w ith another anti-CD98 mAb, HBJ 127, polykaryocyte formation was not detecte d, although extensive cell aggregation was induced, When HBJ 127 and 6-1-13 were simultaneously added to the culture fluids, anti-CD98 mAb-induced cel l fusion was inhibited almost completely. HBJ 127 suppressed formation of 6 -1-13-induced cell fusion in a dose-dependent manner. Lf,however, HBJ 127 w as added after incubation of monocytes with mAb 6-1-13 for 6 h, an apprecia ble degree of TRAP-positive polykaryocyte formation was found. The bindings of 6-1-13 and HBJ 127 were not mutually competed. When monocytes mere incu bated with 6-1-13 or HBJ 127, 6-1-13 induced c-src mRNA, while HBJ 127 did not. Furthermore, when monocytes were incubated with both 6-1-13 and HBJ 12 7, c-src mRNA could not be detected, showing that HBJ 127 suppresses c-src expression. Therefore, CD98-mediated osteoclast formation can be regulated by modification of CD98 system. (C) 1999 Academic Press.