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PMID: 9950424 Published · ppublish English Journal Article

OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis.

Nature ·Vol. 397 ·No. 6717 ·1999-01-28 ·Pages 315-23

Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM

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,genetics,physiology Dendritic Cells/cytology Embryonic and Fetal Development/physiology Female Gene Targeting Growth Substances/genetics,physiology Hematopoiesis, Extramedullary Hematopoietic Stem Cells/cytology Leukopoiesis/physiology Lymph Nodes/abnormalities,embryology Lymphocyte Activation Lymphocytes/cytology,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,immunology Thymus Gland/cytology,embryology

Chemicals

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

Authors & Affiliations

17 authors, click to expand affiliations / ORCID

Kong Y Y

Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada.

Yoshida H

Sarosi I

Tan H L

Timms E

Capparelli C

Morony S

Oliveira-dos-Santos A J

Van G

Itie A

Khoo W

Wakeham A

Dunstan C R

Lacey D L

Mak T W

Boyle W J

Penninger J M

Article Info

Journal

Nature

Abbr.

Nature

ISSN

0028-0836

DOI

10.1038/16852

Published

1999-01-28

Pages

315-23

Language

English

Region

England

NLM ID

0410462

Subset

Databases

GENBANK

AF053713

External Links

PubMed source DOI: 10.1038/16852 View journal details

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OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis.

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