Cell-to-Cell adhesion via intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 pathway is involved in 1alpha,25(OH)2D3, PTH and IL-1alpha-induced osteoclast differentiation and bone resorption

Endocr J. 2002 Aug;49(4):483-95. doi: 10.1507/endocrj.49.483.

Abstract

Cell-to-cell interaction is required for the differentiation of osteoclast precursors as well as for osteoclast function. The present study was undertaken to determine whether 1,25 dihydroxyvitamin D3 (1,25D), PTH, IL-1alpha and PGE2 depend on cell-to-cell interactions through the intercellular adhesion molecule (ICAM)-1/leukocyte function-associated antigen (LFA)-1 pathway in osteoclast formation and bone resorption. We found that mouse osteoblasts expressed ICAM-1 and that the expression was increased by treatment with PTH, IL-1alpha or 1,25D, but not by PGE2. In resorption assays measuring either 45Ca release from bone organ cultures or pit formation in bone cell cultures, 1,25D-, PTH- and IL-1alpha-stimulated resorption was inhibited by anti-ICAM-1 monoclonal antibody (mAb) and/or anti-LFA-1 mAb, while basal and PGE2-stimulated bone resorbing activities were not affected by these mAbs. Furthermore, in a mouse bone marrow culture system, stimulation of osteoclast-like (OCL) cell formation by 1,25D (10 nM), PTH (10 ng/ml) or IL-1alpha (10 ng/ml) was inhibited by the addition of anti-ICAM-1 mAb and/or anti-LFA-1 mAb. In a coculture system of murine spleen cells and osteoblasts, the ICAM-1/LFA-1 interaction was also involved in 1,25D-, PTH- and IL-1alpha-stimulated TRAP-positive MNC formation. However, anti-ICAM-1 mAb and anti-LFA-1 mAb did not alter either 1,25D- or PTH-stimulated receptor activator of NF-kappaB ligand (RANKL) mRNA transcription in bone marrow cultures. Taken together, we here propose that ICAM-1-mediated cell-to-cell adhesion of osteoblasts and osteoclast precursors is involved in RANKL-dependent osteoclast maturation stimulated by 1,25D, PTH, and IL-1alpha.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Bone Marrow Cells / metabolism
  • Bone Resorption / physiopathology*
  • Calcitriol / pharmacology*
  • Carrier Proteins / genetics
  • Cell Adhesion / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Coculture Techniques
  • Glycoproteins / genetics
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-1 / pharmacology*
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Membrane Glycoproteins / genetics
  • Mice
  • Osteoblasts / cytology*
  • Osteoblasts / physiology*
  • Osteoprotegerin
  • Parathyroid Hormone / pharmacology*
  • RANK Ligand
  • RNA, Messenger / metabolism
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Tumor Necrosis Factor

Substances

  • Antibodies, Monoclonal
  • Carrier Proteins
  • Glycoproteins
  • Interleukin-1
  • Lymphocyte Function-Associated Antigen-1
  • Membrane Glycoproteins
  • Osteoprotegerin
  • Parathyroid Hormone
  • RANK Ligand
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf11a protein, mouse
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Intercellular Adhesion Molecule-1
  • Calcitriol