Mori K, Miyamoto N, Higuchi Y, Nanba K, Ito M, Tsurudome M, Nishio M, Kawano M, Uchida A, Ito Y
Department of Microbiology, Mie University School of Medicine, 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514-8507, Japan.
Cell Immunol. 2001 Feb 1;207(2):118-26. doi: 10.1006/cimm.2000.1748.
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.
最近报道了破骨细胞生成的两条途径，即RANKL介导的和CD98介导的破骨细胞生成。在新鲜分离的单核细胞或与抗FRP-1/CD98hc抗体孵育的单核细胞中未发现RANKL、OCIF和TIMP-3 mRNA。在这些细胞中可检测到RANK、TACE和M-CSF mRNA。有趣的是，用抗CD98hc抗体培养单核细胞可使RANK mRNA的表达量增加，且在破骨细胞样细胞中观察到最大表达。OCIF可阻断CD98介导的细胞聚集和多核巨细胞形成。OCIF还可抑制单核细胞中CD98介导的Sp1和c-src mRNA的诱导。可溶性RANK对CD98介导的细胞聚集和多核巨细胞形成无影响。当血液单核细胞与RANKL和M-CSF孵育时，在与这些细胞因子孵育7天的血液单核细胞中首先发现c-src和Sp1 mRNA。相反，用抗CD98hc mAb处理血液单核细胞3小时后即可检测到c-src mRNA。未发现LAT-1 mRNA，在未用或用抗CD98hc mAb或RANKL和M-CSF刺激的单核细胞中，Y(+)LAT-1和Y(+)LAT-2 mRNA的表达水平未发生变化。一种针对CD98hc的抑制性mAb，HBJ 127，对RANKL介导的细胞聚集和细胞融合具有抑制作用。因此，这两条途径之间存在相互作用。
