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L-caldesmon alters cell spreading and adhesion force in RANKL-induced osteoclasts
BACKGROUND: Osteoclasts (OCs) are motile multinucleated cells derived from differentiation and fusion of hematopoietic progenitors of the monocyte-macrophage lineage that undergo a multistep process called osteoclastogenesis. The biological function of OCs is to resorb bone matrix for controlling bo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345023/ https://www.ncbi.nlm.nih.gov/pubmed/30678675 http://dx.doi.org/10.1186/s12929-019-0505-1 |
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author | Chan, Chu-Lung Chen, Jiann-Yeu Shih, Ming-Chih Wang, Chih-Lueh Albert Liou, Ying-Ming |
author_facet | Chan, Chu-Lung Chen, Jiann-Yeu Shih, Ming-Chih Wang, Chih-Lueh Albert Liou, Ying-Ming |
author_sort | Chan, Chu-Lung |
collection | PubMed |
description | BACKGROUND: Osteoclasts (OCs) are motile multinucleated cells derived from differentiation and fusion of hematopoietic progenitors of the monocyte-macrophage lineage that undergo a multistep process called osteoclastogenesis. The biological function of OCs is to resorb bone matrix for controlling bone strength and integrity, which is essential for bone development. The bone resorption function is based on the remodelling of the actin cytoskeleton into an F-actin-rich structure known as the sealing zone for bone anchoring and matrix degradation. Non-muscle caldesmon (l-CaD) is known to participate in the regulation of actin cytoskeletal remodeling, but its function in osteoclastogenesis remains unclear. METHODS/RESULTS: In this study, gain and loss of the l-CaD level in RAW264.7 murine macrophages followed by RANKL induction was used as an experimental approach to examine the involvement of l-CaD in the control of cell fusion into multinucleated OCs in osteoclastogenesis. In comparison with controls, l-CaD overexpression significantly increased TRAP activity, actin ring structure and mineral substrate resorption in RANKL-induced cells. In contrast, gene silencing against l-CaD decreased the potential for RANKL-induced osteoclastogenesis and mineral substrate resorption. In addition, OC precursor cells with l-CaD overexpression and gene silencing followed by RANKL induction caused 13% increase and 24% decrease, respectively, in cell fusion index. To further understand the mechanistic action of l-CaD in the modulation of OC fusion, atomic force microscopy was used to resolve the mechanical changes of cell spreading and adhesion force in RANKL-induced cells with and without l-CaD overexpression or gene silencing. CONCLUSIONS: l-CaD plays a key role in the regulation of actin cytoskeletal remodeling for the formation of actin ring structure at the cell periphery, which may in turn alter the mechanical property of cell-spreading and cell surface adhesion force, thereby facilitating cell-cell fusion into multinucleated OCs during osteoclastogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-019-0505-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6345023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63450232019-01-29 L-caldesmon alters cell spreading and adhesion force in RANKL-induced osteoclasts Chan, Chu-Lung Chen, Jiann-Yeu Shih, Ming-Chih Wang, Chih-Lueh Albert Liou, Ying-Ming J Biomed Sci Research BACKGROUND: Osteoclasts (OCs) are motile multinucleated cells derived from differentiation and fusion of hematopoietic progenitors of the monocyte-macrophage lineage that undergo a multistep process called osteoclastogenesis. The biological function of OCs is to resorb bone matrix for controlling bone strength and integrity, which is essential for bone development. The bone resorption function is based on the remodelling of the actin cytoskeleton into an F-actin-rich structure known as the sealing zone for bone anchoring and matrix degradation. Non-muscle caldesmon (l-CaD) is known to participate in the regulation of actin cytoskeletal remodeling, but its function in osteoclastogenesis remains unclear. METHODS/RESULTS: In this study, gain and loss of the l-CaD level in RAW264.7 murine macrophages followed by RANKL induction was used as an experimental approach to examine the involvement of l-CaD in the control of cell fusion into multinucleated OCs in osteoclastogenesis. In comparison with controls, l-CaD overexpression significantly increased TRAP activity, actin ring structure and mineral substrate resorption in RANKL-induced cells. In contrast, gene silencing against l-CaD decreased the potential for RANKL-induced osteoclastogenesis and mineral substrate resorption. In addition, OC precursor cells with l-CaD overexpression and gene silencing followed by RANKL induction caused 13% increase and 24% decrease, respectively, in cell fusion index. To further understand the mechanistic action of l-CaD in the modulation of OC fusion, atomic force microscopy was used to resolve the mechanical changes of cell spreading and adhesion force in RANKL-induced cells with and without l-CaD overexpression or gene silencing. CONCLUSIONS: l-CaD plays a key role in the regulation of actin cytoskeletal remodeling for the formation of actin ring structure at the cell periphery, which may in turn alter the mechanical property of cell-spreading and cell surface adhesion force, thereby facilitating cell-cell fusion into multinucleated OCs during osteoclastogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-019-0505-1) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-24 /pmc/articles/PMC6345023/ /pubmed/30678675 http://dx.doi.org/10.1186/s12929-019-0505-1 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Chan, Chu-Lung Chen, Jiann-Yeu Shih, Ming-Chih Wang, Chih-Lueh Albert Liou, Ying-Ming L-caldesmon alters cell spreading and adhesion force in RANKL-induced osteoclasts |
title | L-caldesmon alters cell spreading and adhesion force in RANKL-induced osteoclasts |
title_full | L-caldesmon alters cell spreading and adhesion force in RANKL-induced osteoclasts |
title_fullStr | L-caldesmon alters cell spreading and adhesion force in RANKL-induced osteoclasts |
title_full_unstemmed | L-caldesmon alters cell spreading and adhesion force in RANKL-induced osteoclasts |
title_short | L-caldesmon alters cell spreading and adhesion force in RANKL-induced osteoclasts |
title_sort | l-caldesmon alters cell spreading and adhesion force in rankl-induced osteoclasts |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345023/ https://www.ncbi.nlm.nih.gov/pubmed/30678675 http://dx.doi.org/10.1186/s12929-019-0505-1 |
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