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Identification of Novel Genes for Cell Fusion during Osteoclast Formation
Osteoclasts are derived from hematopoietic stem cells. Monocyte preosteoclasts obtain resorbing activity via cell–cell fusion to generate multinucleated cells. However, the mechanisms and molecules involved in the fusion process are poorly understood. In this study, we performed RNA sequencing with...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224196/ https://www.ncbi.nlm.nih.gov/pubmed/35742859 http://dx.doi.org/10.3390/ijms23126421 |
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author | Cho, Eunjin Cheon, Seongmin Ding, Mina Lim, Kayeong Park, Sang-Wook Park, Chungoo Lee, Tae-Hoon |
author_facet | Cho, Eunjin Cheon, Seongmin Ding, Mina Lim, Kayeong Park, Sang-Wook Park, Chungoo Lee, Tae-Hoon |
author_sort | Cho, Eunjin |
collection | PubMed |
description | Osteoclasts are derived from hematopoietic stem cells. Monocyte preosteoclasts obtain resorbing activity via cell–cell fusion to generate multinucleated cells. However, the mechanisms and molecules involved in the fusion process are poorly understood. In this study, we performed RNA sequencing with single nucleated cells (SNCs) and multinucleated cells (MNCs) to identify the fusion-specific genes. The SNCs and MNCs were isolated under the same conditions during osteoclastogenesis with the receptor activator of nuclear factor-κB ligand (RANKL) administration. Based on this analysis, the expression of seven genes was found to be significantly increased in MNCs but decreased in SNCs, compared to that in bone marrow-derived macrophages (BMMs). We then generated knockout macrophage cell lines using a CRISPR-Cas9 genome-editing tool to examine their function during osteoclastogenesis. Calcrl-, Marco-, or Ube3a-deficient cells could not develop multinucleated giant osteoclasts upon RANKL stimulation. However, Tmem26-deficient cells fused more efficiently than control cells. Our findings demonstrate that Calcrl, Marco, and Ube3a are novel determinants of osteoclastogenesis, especially with respect to cell fusion, and highlight potential targets for osteoporosis therapy. |
format | Online Article Text |
id | pubmed-9224196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92241962022-06-24 Identification of Novel Genes for Cell Fusion during Osteoclast Formation Cho, Eunjin Cheon, Seongmin Ding, Mina Lim, Kayeong Park, Sang-Wook Park, Chungoo Lee, Tae-Hoon Int J Mol Sci Article Osteoclasts are derived from hematopoietic stem cells. Monocyte preosteoclasts obtain resorbing activity via cell–cell fusion to generate multinucleated cells. However, the mechanisms and molecules involved in the fusion process are poorly understood. In this study, we performed RNA sequencing with single nucleated cells (SNCs) and multinucleated cells (MNCs) to identify the fusion-specific genes. The SNCs and MNCs were isolated under the same conditions during osteoclastogenesis with the receptor activator of nuclear factor-κB ligand (RANKL) administration. Based on this analysis, the expression of seven genes was found to be significantly increased in MNCs but decreased in SNCs, compared to that in bone marrow-derived macrophages (BMMs). We then generated knockout macrophage cell lines using a CRISPR-Cas9 genome-editing tool to examine their function during osteoclastogenesis. Calcrl-, Marco-, or Ube3a-deficient cells could not develop multinucleated giant osteoclasts upon RANKL stimulation. However, Tmem26-deficient cells fused more efficiently than control cells. Our findings demonstrate that Calcrl, Marco, and Ube3a are novel determinants of osteoclastogenesis, especially with respect to cell fusion, and highlight potential targets for osteoporosis therapy. MDPI 2022-06-08 /pmc/articles/PMC9224196/ /pubmed/35742859 http://dx.doi.org/10.3390/ijms23126421 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cho, Eunjin Cheon, Seongmin Ding, Mina Lim, Kayeong Park, Sang-Wook Park, Chungoo Lee, Tae-Hoon Identification of Novel Genes for Cell Fusion during Osteoclast Formation |
title | Identification of Novel Genes for Cell Fusion during Osteoclast Formation |
title_full | Identification of Novel Genes for Cell Fusion during Osteoclast Formation |
title_fullStr | Identification of Novel Genes for Cell Fusion during Osteoclast Formation |
title_full_unstemmed | Identification of Novel Genes for Cell Fusion during Osteoclast Formation |
title_short | Identification of Novel Genes for Cell Fusion during Osteoclast Formation |
title_sort | identification of novel genes for cell fusion during osteoclast formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224196/ https://www.ncbi.nlm.nih.gov/pubmed/35742859 http://dx.doi.org/10.3390/ijms23126421 |
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