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.
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.
Department of Microbiology, Mie University School of Medicine, 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514-8507, Japan.
K
K
Mori
N
N
Miyamoto
Y
Y
Higuchi
K
K
Nanba
M
M
Ito
M
M
Tsurudome
M
M
Nishio
M
M
Kawano
A
A
Uchida
Y
Y
Ito
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D000081247:CSK Tyrosine-Protein Kinase; D002352:Carrier Proteins / Q000494:pharmacology* / Q000502:physiology*; D002449:Cell Aggregation; D002459:Cell Fusion; D027261:Fusion Regulatory Protein-1; D006023:Glycoproteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology* / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D016329:Sp1 Transcription Factor / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019061:src-Family Kinases
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D016329:Sp1 Transcription Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505653:TNFSF10 protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human