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PMID: 7595216 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interleukin (IL)-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors.

The Journal of experimental medicine ·Vol. 182 ·No. 5 ·1995-11-01 ·Pages 1461-8

Udagawa N, Takahashi N, Katagiri T, Tamura T, Wada S, Findlay DM, Martin TJ, Hirota H, Taga T, Kishimoto T, Suda T

Abstract

We reported that interleukin (IL) 6 alone cannot induce osteoclast formation in cocultures of mouse bone marrow and osteoblastic cells, but soluble IL-6 receptor (IL-6R) strikingly triggered osteoclast formation induced by IL-6. In this study, we examined the mechanism of osteoclast formation by IL-6 and related cytokines through the interaction between osteoblastic cells and osteoclast progenitors. When dexamethasone was added to the cocultures, IL-6 could stimulate osteoclast formation without the help of soluble IL-6R. Osteoblastic cells expressed a very low level of IL-6R mRNA, whereas fresh mouse spleen and bone marrow cells, both of which are considered to be osteoclast progenitors, constitutively expressed relatively high levels of IL-6R mRNA. Treatment of osteoblastic cells with dexamethasone induced a marked increase in the expression of IL-6R mRNA. By immunoblotting with antiphosphotyrosine antibody, IL-6 did not tyrosine-phosphorylate a protein with a molecular mass of 130 kD in osteoblastic cells but did so in dexamethasone-pretreated osteoblastic cells. Osteoblastic cells from transgenic mice constitutively expressing human IL-6R could support osteoclast development in the presence of human IL-6 alone in cocultures with normal spleen cells. In contrast, osteoclast progenitors in spleen cells from transgenic mice overexpressing human IL-6R were not able to differentiate into osteoclasts in response to IL-6 in cocultures with normal osteoblastic cells. These results clearly indicate that the ability of IL-6 to induce osteoclast differentiation depends on signal transduction mediated by IL-6R expressed on osteoblastic cells but not on osteoclast progenitors.

MeSH Terms
Animals Antigens, CD/biosynthesis,genetics,physiology Bone Marrow Cells Cell Differentiation/drug effects Coculture Techniques Dexamethasone/pharmacology Humans Interleukin-6/pharmacology Male Mice Mice, Inbred Strains Mice, Transgenic Osteoblasts/cytology,drug effects,metabolism Osteoclasts/metabolism Phosphorylation Protein Processing, Post-Translational Protein-Tyrosine Kinases/metabolism RNA, Messenger/biosynthesis Receptors, Interleukin/biosynthesis,genetics,physiology Receptors, Interleukin-6 Recombinant Proteins/biosynthesis Signal Transduction Skull/cytology Spleen/cytology Stem Cells/cytology,drug effects,metabolism Up-Regulation
Chemicals
Antigens, CD Interleukin-6 RNA, Messenger Receptors, Interleukin Receptors, Interleukin-6 Recombinant Proteins Dexamethasone Protein-Tyrosine Kinases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Udagawa N
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
Takahashi N
Katagiri T
Tamura T
Wada S
Findlay D M
Martin T J
Hirota H
Taga T
Kishimoto T
Suda T
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.182.5.1461
Published
1995-11-01
Pages
1461-8
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192181
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.182.5.1461 PMC Full Text View journal details
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