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PMID: 8676079 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures.

The Journal of experimental medicine ·Vol. 183 ·No. 6 ·1996-06-01 ·Pages 2581-91

Romas E, Udagawa N, Zhou H, Tamura T, Saito M, Taga T, Hilton DJ, Suda T, Ng KW, Martin TJ

Abstract

Interleukin (IL)-11 is a multifunctional cytokine whose role in osteoclast development has not been fully elucidated. We examined IL-11 production by primary osteoblasts and the effects of rat monoclonal anti-mouse glycoprotein 130 (gp130) antibody on osteoclast formation, using a coculture of mouse osteoblasts and bone marrow cells. IL-1, TNF alpha, PGE2, parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) similarly induced production of IL-11 by osteoblasts, but IL-6, IL-4, and TGF beta did not. Primary osteoblasts constitutively expressed mRNAs for both IL-11 receptor (IL-11R alpha) and gp130. Osteotropic factors did not modulate IL-11R alpha mRNA at 24 h, but steady-state gp130 mRNA expression in osteoblasts was upregulated by 1 alpha,25(OH)2D3, PTH, or IL-1. In cocultures, the formation of multinucleated osteoclast-like cells (OCLs) in response to IL-11, or IL-6 together with its soluble IL-6 receptor was dose-dependently inhibited by rat monoclonal anti-mouse gp130 antibody. Furthermore, adding anti-gp130 antibody abolished OCL formation induced by IL-1, and partially inhibited OCL formation induced by PGE2, PTH, or 1 alpha,25(OH)2D3. During osteoclast formation in marrow cultures, a sequential relationship existed between the expression of calcitonin receptor mRNA and IL-11R alpha mRNA. Osteoblasts as well as OCLs expressed transcripts for IL-11R alpha, as indicated by RT-PCR analysis and in situ hybridization. These results suggest a central role of gp130-coupled cytokines, especially IL-11, in osteoclast development. Since osteoblasts and mature osteoclasts expressed IL-11R alpha mRNA, both bone-forming and bone-resorbing cells are potential targets of IL-11.

MeSH Terms
Animals Animals, Newborn Antibodies, Monoclonal/pharmacology Antigens, CD/immunology,physiology Base Sequence Bone Marrow/immunology Bone Marrow Cells Calcitriol/pharmacology Cells, Cultured Coculture Techniques Cytokine Receptor gp130 Cytokines/pharmacology DNA Primers Dinoprostone/pharmacology Humans In Situ Hybridization Interleukin-1/pharmacology Interleukin-11/biosynthesis Interleukin-11 Receptor alpha Subunit Kinetics Male Membrane Glycoproteins/immunology,physiology Mice Mice, Inbred C57BL Molecular Sequence Data Osteoblasts/cytology,drug effects,immunology Parathyroid Hormone/pharmacology Polymerase Chain Reaction RNA, Messenger/biosynthesis Rats Receptors, Interleukin/metabolism Receptors, Interleukin-11 Recombinant Proteins/pharmacology Signal Transduction Time Factors Transcription, Genetic Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Antibodies, Monoclonal Antigens, CD Cytokines DNA Primers IL11RA protein, human IL6ST protein, human Il11ra1 protein, mouse Il11ra1 protein, rat Il11ra2 protein, mouse Il6st protein, mouse Il6st protein, rat Interleukin-1 Interleukin-11 Interleukin-11 Receptor alpha Subunit Membrane Glycoproteins Parathyroid Hormone RNA, Messenger Receptors, Interleukin Receptors, Interleukin-11 Recombinant Proteins Tumor Necrosis Factor-alpha Cytokine Receptor gp130 Calcitriol Dinoprostone
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Romas E
St. Vincent's Institute of Medical Research, University of Melbourne, Victoria, Australia.
Udagawa N
Zhou H
Tamura T
Saito M
Taga T
Hilton D J
Suda T
Ng K W
Martin T J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.183.6.2581
Published
1996-06-01
Pages
2581-91
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192607
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.183.6.2581 PMC Full Text View journal details
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