OPGL Is a Key Regulator of Osteoclastogenesis, Lymphocyte Development and Lymph-Node Organogenesis

Nature. 1999 Jan 28;397(6717):315-23. doi: 10.1038/16852.

Abstract

The tumour-necrosis-factor-family molecule osteoprotegerin ligand (OPGL; also known as TRANCE, RANKL and ODF) has been identified as a potential osteoclast differentiation factor and regulator of interactions between T cells and dendritic cells in vitro. Mice with a disrupted opgl gene show severe osteopetrosis and a defect in tooth eruption, and completely lack osteoclasts as a result of an inability of osteoblasts to support osteoclastogenesis. Although dendritic cells appear normal, opgl-deficient mice exhibit defects in early differentiation of T and B lymphocytes. Surprisingly, opgl-deficient mice lack all lymph nodes but have normal splenic structure and Peyer's patches. Thus OPGL is a new regulator of lymph-node organogenesis and lymphocyte development and is an essential osteoclast differentiation factor in vivo.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • Bone Remodeling / physiology
  • Carrier Proteins*
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytokines / physiology*
  • Dendritic Cells / cytology
  • Embryonic and Fetal Development / physiology*
  • Female
  • Gene Targeting
  • Growth Substances / genetics
  • Growth Substances / physiology*
  • Hematopoiesis, Extramedullary
  • Hematopoietic Stem Cells / cytology
  • Leukopoiesis / physiology
  • Lymph Nodes / abnormalities
  • Lymph Nodes / embryology*
  • Lymphocyte Activation
  • Lymphocytes / cytology*
  • Lymphocytes / immunology
  • Male
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutagenesis
  • Osteoclasts / cytology*
  • Osteogenesis / physiology*
  • Osteopetrosis / genetics
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology
  • Thymus Gland / embryology

Substances

  • Carrier Proteins
  • Cytokines
  • Growth Substances
  • Membrane Glycoproteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse

Associated data

  • GENBANK/AF053713