Lyn inhibits osteoclast differentiation by interfering with PLCγ1-mediated Ca2+ signaling

Soo Hyun Yoon; Youngkyun Lee; Hyung Joon Kim; Zang Hee Lee; Seok Won Hyung; Sang Won Lee; Hong Hee Kim

doi:10.1016/j.febslet.2009.03.005

Lyn inhibits osteoclast differentiation by interfering with PLCγ1-mediated Ca²⁺ signaling

Soo Hyun Yoon, Youngkyun Lee, Hyung Joon Kim, Zang Hee Lee, Seok Won Hyung, Sang Won Lee, Hong Hee Kim

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

Osteoclasts differentiate from macrophage-lineage cells to become specialized for bone resorption function. By a proteomics approach, we found that Lyn was down-regulated by the osteoclast differentiation factor, receptor activator of NF-κB ligand (RANKL). The forced reduction of Lyn caused a striking increase in the RANKL-induced PLCγ1, Ca²⁺, and NFATc1 responses during differentiation. These data suggest that Lyn plays a negative role in osteoclastogenesis by interfering with the PLCγ1-mediated Ca²⁺ signaling that leads to NFATc1 activation. Consistent with the in vitro results, in vivo injection of Lyn specific siRNA into mice calvariae provoked a fulminant bone resorption. Our study provides the first evidence of the involvement of Lyn in the negative regulation of osteoclastogenesis by RANKL.

Original language	English
Pages (from-to)	1164-1170
Number of pages	7
Journal	FEBS Letters
Volume	583
Issue number	7
DOIs	https://doi.org/10.1016/j.febslet.2009.03.005
Publication status	Published - 2009 Apr 2

Bibliographical note

Funding Information:
This work was supported by 21C Frontier Functional Proteomics Project (FPR08B1-170), New Drug Target Discovery (M10748000257-07N4800-25710), and Science Research Center (R11-2008-023-01001-0) grants.

Keywords

Lyn
Osteoclast
RANKL

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

Access to Document

10.1016/j.febslet.2009.03.005

Cite this

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title = "Lyn inhibits osteoclast differentiation by interfering with PLCγ1-mediated Ca2+ signaling",

abstract = "Osteoclasts differentiate from macrophage-lineage cells to become specialized for bone resorption function. By a proteomics approach, we found that Lyn was down-regulated by the osteoclast differentiation factor, receptor activator of NF-κB ligand (RANKL). The forced reduction of Lyn caused a striking increase in the RANKL-induced PLCγ1, Ca2+, and NFATc1 responses during differentiation. These data suggest that Lyn plays a negative role in osteoclastogenesis by interfering with the PLCγ1-mediated Ca2+ signaling that leads to NFATc1 activation. Consistent with the in vitro results, in vivo injection of Lyn specific siRNA into mice calvariae provoked a fulminant bone resorption. Our study provides the first evidence of the involvement of Lyn in the negative regulation of osteoclastogenesis by RANKL.",

keywords = "Lyn, Osteoclast, RANKL",

author = "Yoon, {Soo Hyun} and Youngkyun Lee and Kim, {Hyung Joon} and Lee, {Zang Hee} and Hyung, {Seok Won} and Lee, {Sang Won} and Kim, {Hong Hee}",

note = "Funding Information: This work was supported by 21C Frontier Functional Proteomics Project (FPR08B1-170), New Drug Target Discovery (M10748000257-07N4800-25710), and Science Research Center (R11-2008-023-01001-0) grants.",

year = "2009",

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doi = "10.1016/j.febslet.2009.03.005",

language = "English",

volume = "583",

pages = "1164--1170",

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T1 - Lyn inhibits osteoclast differentiation by interfering with PLCγ1-mediated Ca2+ signaling

AU - Yoon, Soo Hyun

AU - Lee, Youngkyun

AU - Kim, Hyung Joon

AU - Lee, Zang Hee

AU - Hyung, Seok Won

AU - Lee, Sang Won

AU - Kim, Hong Hee

N1 - Funding Information: This work was supported by 21C Frontier Functional Proteomics Project (FPR08B1-170), New Drug Target Discovery (M10748000257-07N4800-25710), and Science Research Center (R11-2008-023-01001-0) grants.

PY - 2009/4/2

Y1 - 2009/4/2

N2 - Osteoclasts differentiate from macrophage-lineage cells to become specialized for bone resorption function. By a proteomics approach, we found that Lyn was down-regulated by the osteoclast differentiation factor, receptor activator of NF-κB ligand (RANKL). The forced reduction of Lyn caused a striking increase in the RANKL-induced PLCγ1, Ca2+, and NFATc1 responses during differentiation. These data suggest that Lyn plays a negative role in osteoclastogenesis by interfering with the PLCγ1-mediated Ca2+ signaling that leads to NFATc1 activation. Consistent with the in vitro results, in vivo injection of Lyn specific siRNA into mice calvariae provoked a fulminant bone resorption. Our study provides the first evidence of the involvement of Lyn in the negative regulation of osteoclastogenesis by RANKL.

AB - Osteoclasts differentiate from macrophage-lineage cells to become specialized for bone resorption function. By a proteomics approach, we found that Lyn was down-regulated by the osteoclast differentiation factor, receptor activator of NF-κB ligand (RANKL). The forced reduction of Lyn caused a striking increase in the RANKL-induced PLCγ1, Ca2+, and NFATc1 responses during differentiation. These data suggest that Lyn plays a negative role in osteoclastogenesis by interfering with the PLCγ1-mediated Ca2+ signaling that leads to NFATc1 activation. Consistent with the in vitro results, in vivo injection of Lyn specific siRNA into mice calvariae provoked a fulminant bone resorption. Our study provides the first evidence of the involvement of Lyn in the negative regulation of osteoclastogenesis by RANKL.

KW - Lyn

KW - Osteoclast

KW - RANKL

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