7th World Congress On Inflammation, Melbourne , 2005-11-20

Title : ( Transforming Growth Factor Beta Inhibits Osteoclast Formation Via The Down Regulation Of c-Fos )

Authors: Roya Lari , Peter D. Kitchenerb , John A. Hamiltona ,

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Abstract

Bone loss is one of the major pathological symptoms of inflammatory condition, which is the consequence of induction of osteoclast differentiation and activation. Transforming growth factor-β (TGF-β) is the most abundant growth factor in bone that has a variety of immunoregulatory and anti-inflammatory activities. To gain better understanding of the complex role of TGF-β in osteoclastogenesis, we have investigated direct effects of TGF-β on osteoclast differentiation by M-CSF and RANKL from bone marrow derive macrophages. TGF-β significantly suppressed the : of osteoclast precursors (P values<0.01) and also inhibited the differentiation of bone marrow derive macrophages to osteoclast in a dosage dependent manner. At the high concentration (10 ng/ml), it abridged number of TRAP+ cells (P values<0.01) and also down regulated the osteoclastic genes expression of CTR, Cath k as measured by Q-PCR. Although, TGF-β did not have any effect on gene expression of RANK and c-Fms, but it suppressed the induction of c-Fos gene (an essential transcription factor for osteoclast differentiation) expression by M-CSF and RANKL. Also, GM-CSF-/-, IL-10-/- and interferon receptor 1and 2 knock out mice have been employed to investigate the involvement of endogenous inhibitory factors of GM-CSF, IL-10 and type one interferon in the inhibitory effect of TGF-β. No significant effects were observed in any of those mice compare with wild type. Our data suggests that TGF-β directly act as a negative regulatory factor for the formation of osteoclast by two different mechanisms. Firstly, by reducing the number of osteoclast precursors and secondly by down regulation of c-Fos expression.

Keywords

, Transforming growth factor, β; inflammatory; osteoclast; proliferation; c, Fos
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@inproceedings{paperid:1020114,
author = {Lari, Roya and Peter D. Kitchenerb and John A. Hamiltona},
title = {Transforming Growth Factor Beta Inhibits Osteoclast Formation Via The Down Regulation Of c-Fos},
booktitle = {7th World Congress On Inflammation, Melbourne},
year = {2005},
location = {Melbourne, AUSTRALIA},
keywords = {Transforming growth factor-β; inflammatory; osteoclast; proliferation; c-Fos},
}

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%0 Conference Proceedings
%T Transforming Growth Factor Beta Inhibits Osteoclast Formation Via The Down Regulation Of c-Fos
%A Lari, Roya
%A Peter D. Kitchenerb
%A John A. Hamiltona
%J 7th World Congress On Inflammation, Melbourne
%D 2005

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