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

Cell Immunol. 2001 Feb 1;207(2):118-26. doi: 10.1006/cimm.2000.1748.

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.

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antigens, CD / physiology*
  • Apoptosis Regulatory Proteins
  • CSK Tyrosine-Protein Kinase
  • Carrier Proteins / pharmacology*
  • Carrier Proteins / physiology*
  • Cell Aggregation
  • Cell Fusion
  • Fusion Regulatory Protein-1
  • Glycoproteins / genetics
  • Glycoproteins / pharmacology*
  • Glycoproteins / physiology
  • Humans
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Membrane Glycoproteins / pharmacology*
  • Membrane Glycoproteins / physiology
  • Osteoclasts / physiology*
  • Osteoprotegerin
  • Protein-Tyrosine Kinases / genetics
  • RANK Ligand
  • RNA, Messenger / analysis
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Receptors, Tumor Necrosis Factor
  • Sp1 Transcription Factor / genetics
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / physiology
  • src-Family Kinases

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Fusion Regulatory Protein-1
  • Glycoproteins
  • Membrane Glycoproteins
  • Osteoprotegerin
  • RANK Ligand
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • Sp1 Transcription Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF10 protein, human
  • TNFSF11 protein, human
  • Tumor Necrosis Factor-alpha
  • Macrophage Colony-Stimulating Factor
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human