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  • Title: Cross-talk between RANKL and FRP-1/CD98 Systems: RANKL-mediated osteoclastogenesis is suppressed by an inhibitory anti-CD98 heavy chain mAb and CD98-mediated osteoclastogenesis is suppressed by osteoclastogenesis inhibitory factor.
    Author: Mori K, Miyamoto N, Higuchi Y, Nanba K, Ito M, Tsurudome M, Nishio M, Kawano M, Uchida A, Ito Y.
    Journal: Cell Immunol; 2001 Feb 01; 207(2):118-26. PubMed ID: 11243701.
    Abstract:
    The two pathways to osteoclastogenesis, RANKL-mediated and CD98-mediated osteoclastogenesis, have recently been reported. RANKL, OCIF, and TIMP-3 mRNAs are not found in monocytes freshly isolated or incubated with anti-FRP-1/CD98hc antibody. RANK, TACE, and M-CSF mRNAs can be detected in these cells. Interestingly, the expressed amount of RANK mRNA increases by cultivation of monocytes with anti-CD98hc antibody and maximal expression is observed in osteoclast-like cells. CD98-mediated cell aggregation and multinucleated giant cell formation are blocked by OCIF. OCIF also suppressed the CD98-mediated induction of Sp1 and c-src mRNAs in monocytes. Soluble RANK shows no effect on CD98-mediated cell aggregation and multinucleated giant cell formation. When blood monocytes were incubated with RANKL and M-CSF, c-src and Sp1 mRNAs were first found in blood monocytes incubated with these cytokines for 7 days. On the contrary, c-src mRNA could be detected 3 h after treatment of blood monocytes with anti-CD98hc mAb. LAT-1 mRNA was not found, and the expression levels of Y(+)LAT-1 and Y(+)LAT-2 mRNAs were not changed in monocytes stimulated without or with anti-CD98hc mAb or RANKL and M-CSF. An inhibitory mAb directed against CD98hc, HBJ 127, shows a suppressive effect on RANKL-mediated cell aggregation and cell fusion. Thus, there is cross-talk between these two pathways.
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