Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors
Cells with monocyte/macrophage lineage expressing receptor activator of NF-κB (RANK) differentiate into osteoclasts following stimulation with the RANK ligand (RANKL). Cell adhesion signaling is also required for osteoclast differentiation from precursors. However, details of the mechanism by which...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490906/ https://www.ncbi.nlm.nih.gov/pubmed/23139818 http://dx.doi.org/10.1371/journal.pone.0048795 |
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author | Mochizuki, Ayako Takami, Masamichi Miyamoto, Yoichi Nakamaki, Tsuyoshi Tomoyasu, Shigeru Kadono, Yuho Tanaka, Sakae Inoue, Tomio Kamijo, Ryutaro |
author_facet | Mochizuki, Ayako Takami, Masamichi Miyamoto, Yoichi Nakamaki, Tsuyoshi Tomoyasu, Shigeru Kadono, Yuho Tanaka, Sakae Inoue, Tomio Kamijo, Ryutaro |
author_sort | Mochizuki, Ayako |
collection | PubMed |
description | Cells with monocyte/macrophage lineage expressing receptor activator of NF-κB (RANK) differentiate into osteoclasts following stimulation with the RANK ligand (RANKL). Cell adhesion signaling is also required for osteoclast differentiation from precursors. However, details of the mechanism by which cell adhesion signals induce osteoclast differentiation have not been fully elucidated. To investigate the participation of cell adhesion signaling in osteoclast differentiation, mouse bone marrow-derived macrophages (BMMs) were used as osteoclast precursors, and cultured on either plastic cell culture dishes (adherent condition) or the top surface of semisolid methylcellulose gel loaded in culture tubes (non-adherent condition). BMMs cultured under the adherent condition differentiated into osteoclasts in response to RANKL stimulation. However, under the non-adherent condition, the efficiency of osteoclast differentiation was markedly reduced even in the presence of RANKL. These BMMs retained macrophage characteristics including phagocytic function and gene expression profile. Lipopolysaccharide (LPS) and tumor necrosis factor –αTNF-α activated the NF-κB-mediated signaling pathways under both the adherent and non-adherent conditions, while RANKL activated the pathways only under the adherent condition. BMMs highly expressed RANK mRNA and protein under the adherent condition as compared to the non-adherent condition. Also, BMMs transferred from the adherent to non-adherent condition showed downregulated RANK expression within 24 hours. In contrast, transferring those from the non-adherent to adherent condition significantly increased the level of RANK expression. Moreover, interruption of cell adhesion signaling by echistatin, an RGD-containing disintegrin, decreased RANK expression in BMMs, while forced expression of either RANK or TNFR-associated factor 6 (TRAF6) in BMMs induced their differentiation into osteoclasts even under the non-adherent condition. These results suggest that cell adhesion signaling regulates RANK expression in osteoclast precursors. |
format | Online Article Text |
id | pubmed-3490906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34909062012-11-08 Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors Mochizuki, Ayako Takami, Masamichi Miyamoto, Yoichi Nakamaki, Tsuyoshi Tomoyasu, Shigeru Kadono, Yuho Tanaka, Sakae Inoue, Tomio Kamijo, Ryutaro PLoS One Research Article Cells with monocyte/macrophage lineage expressing receptor activator of NF-κB (RANK) differentiate into osteoclasts following stimulation with the RANK ligand (RANKL). Cell adhesion signaling is also required for osteoclast differentiation from precursors. However, details of the mechanism by which cell adhesion signals induce osteoclast differentiation have not been fully elucidated. To investigate the participation of cell adhesion signaling in osteoclast differentiation, mouse bone marrow-derived macrophages (BMMs) were used as osteoclast precursors, and cultured on either plastic cell culture dishes (adherent condition) or the top surface of semisolid methylcellulose gel loaded in culture tubes (non-adherent condition). BMMs cultured under the adherent condition differentiated into osteoclasts in response to RANKL stimulation. However, under the non-adherent condition, the efficiency of osteoclast differentiation was markedly reduced even in the presence of RANKL. These BMMs retained macrophage characteristics including phagocytic function and gene expression profile. Lipopolysaccharide (LPS) and tumor necrosis factor –αTNF-α activated the NF-κB-mediated signaling pathways under both the adherent and non-adherent conditions, while RANKL activated the pathways only under the adherent condition. BMMs highly expressed RANK mRNA and protein under the adherent condition as compared to the non-adherent condition. Also, BMMs transferred from the adherent to non-adherent condition showed downregulated RANK expression within 24 hours. In contrast, transferring those from the non-adherent to adherent condition significantly increased the level of RANK expression. Moreover, interruption of cell adhesion signaling by echistatin, an RGD-containing disintegrin, decreased RANK expression in BMMs, while forced expression of either RANK or TNFR-associated factor 6 (TRAF6) in BMMs induced their differentiation into osteoclasts even under the non-adherent condition. These results suggest that cell adhesion signaling regulates RANK expression in osteoclast precursors. Public Library of Science 2012-11-06 /pmc/articles/PMC3490906/ /pubmed/23139818 http://dx.doi.org/10.1371/journal.pone.0048795 Text en © 2012 Mochizuki et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mochizuki, Ayako Takami, Masamichi Miyamoto, Yoichi Nakamaki, Tsuyoshi Tomoyasu, Shigeru Kadono, Yuho Tanaka, Sakae Inoue, Tomio Kamijo, Ryutaro Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors |
title | Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors |
title_full | Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors |
title_fullStr | Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors |
title_full_unstemmed | Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors |
title_short | Cell Adhesion Signaling Regulates RANK Expression in Osteoclast Precursors |
title_sort | cell adhesion signaling regulates rank expression in osteoclast precursors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490906/ https://www.ncbi.nlm.nih.gov/pubmed/23139818 http://dx.doi.org/10.1371/journal.pone.0048795 |
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