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Macrophage Inflammatory protein-1α Induces Osteoclast Formation by Activation of the MEK/ERK/c-Fos Pathway and Inhibition of the p38MAPK/IRF-3/IFN-β Pathway

Macrophage Inflammatory protein-1α Induces Osteoclast Formation by Activation of the MEK/ERK/c-Fos Pathway and Inhibition of the p38MAPK/IRF-3/IFN-β Pathway

Masanobu Tsubaki, Chisato Kato, Ai Isono, Junichi Kaneko, Misako Isozaki, Takao Satou, Tatsuki Itoh, Yasuhiro Kidera, Yoshihiro Tanimori, Masashi Yanae, Shozo Nishida

J Cell Biochem. 2010 Dec 15;111(6):1661-72.

PMID: 21053363

Abstract:

Multiple myeloma (MM) is a bone disease that affects many individuals. It was recently reported that macrophage inflammatory protein (MIP)-1α is constitutively secreted by MM cells. MIP-1α causes bone destruction through the formation of osteoclasts (OCs). However, the molecular mechanism underlying MIP-1α-induced OC formation is not well understood. In the present study, we attempted to clarify the mechanism whereby MIP-1α induces OC formation in a mouse macrophage-like cell line comprising C7 cells. We found that MIP-1α augmented OC formation in a concentration-dependent manner; moreover, it inhibited IFN-β and ISGF3γ mRNA expression, and IFN-β secretion. MIP-1α increased the expressions of phosphorylated ERK1/2 and c-Fos and decreased those of phosphorylated p38MAPK and IRF-3. We found that the MEK1/2 inhibitor U0126 inhibited OC formation by suppressing the MEK/ERK/c-Fos pathway. SB203580 induced OC formation by upregulating c-fos mRNA expression, and SB203580 was found to inhibit IFN-β and IRF-3 mRNA expressions. The results indicate that MIP-1α induces OC formation by activating and inhibiting the MEK/ERK/c-Fos and p38MAPK/IRF-3 pathways, respectively, and suppressing IFN-β expression. These findings may be useful in the development of an OC inhibitor that targets intracellular signaling factors.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248621	Macrophage Inflammatory Protein-1α from mouse			Price

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