CCR3 deficiency is associated with increased osteoclast activity and reduced cortical bone volume in adult male mice
(2021) In The Journal of biological chemistry 296.- Abstract
Increasing evidence emphasizes the importance of chemokines and chemokine receptors as regulators of bone remodeling. The C-C chemokine receptor 3 (CCR3) is dramatically upregulated during osteoclastogenesis, but the role of CCR3 in osteoclast formation and bone remodeling in adult mice is unknown. Herein, we used bone marrow macrophages derived from adult male CCR3-proficient and CCR3-deficient mice to study the role of CCR3 in osteoclast formation and activity. CCR3 deficiency was associated with formation of giant hypernucleated osteoclasts, enhanced bone resorption when cultured on bone slices, and altered mRNA expression of related chemokine receptors and ligands. In addition, primary mouse calvarial osteoblasts isolated from... (More)
Increasing evidence emphasizes the importance of chemokines and chemokine receptors as regulators of bone remodeling. The C-C chemokine receptor 3 (CCR3) is dramatically upregulated during osteoclastogenesis, but the role of CCR3 in osteoclast formation and bone remodeling in adult mice is unknown. Herein, we used bone marrow macrophages derived from adult male CCR3-proficient and CCR3-deficient mice to study the role of CCR3 in osteoclast formation and activity. CCR3 deficiency was associated with formation of giant hypernucleated osteoclasts, enhanced bone resorption when cultured on bone slices, and altered mRNA expression of related chemokine receptors and ligands. In addition, primary mouse calvarial osteoblasts isolated from CCR3-deficient mice showed increased mRNA expression of the osteoclast activator-related gene, receptor activator of nuclear factor kappa-B ligand, and osteoblast differentiation-associated genes. Microcomputed tomography analyses of femurs from CCR3-deficient mice revealed a bone phenotype that entailed less cortical thickness and volume. Consistent with our in vitro studies, the total number of osteoclasts did not differ between the genotypes in vivo. Moreover, an increased endocortical osteoid mineralization rate and higher trabecular and cortical bone formation rate was displayed in CCR3-deficient mice. Collectively, our data show that CCR3 deficiency influences osteoblast and osteoclast differentiation and that it is associated with thinner cortical bone in adult male mice.
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- author
- Rosendahl, Sara ; Sulniute, Rima ; Eklund, Michaela ; Koskinen Holm, Cecilia ; Johansson, Marcus J O LU ; Kindstedt, Elin ; Lindquist, Susanne and Lundberg, Pernilla
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Bone and Bones/metabolism, Cell Differentiation/physiology, Cells, Cultured, Cortical Bone/metabolism, Disease Models, Animal, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, NF-kappa B/metabolism, Osteoblasts/metabolism, Osteoclasts/metabolism, RANK Ligand/metabolism, Receptors, CCR3/deficiency, X-Ray Microtomography/methods
- in
- The Journal of biological chemistry
- volume
- 296
- article number
- 100177
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- scopus:85102806599
- pmid:33303631
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.RA120.015571
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
- id
- 02a73db3-bf2f-43df-9974-c40232bfd820
- date added to LUP
- 2024-02-28 17:42:58
- date last changed
- 2024-04-14 00:23:07
@article{02a73db3-bf2f-43df-9974-c40232bfd820,
abstract = {{<p>Increasing evidence emphasizes the importance of chemokines and chemokine receptors as regulators of bone remodeling. The C-C chemokine receptor 3 (CCR3) is dramatically upregulated during osteoclastogenesis, but the role of CCR3 in osteoclast formation and bone remodeling in adult mice is unknown. Herein, we used bone marrow macrophages derived from adult male CCR3-proficient and CCR3-deficient mice to study the role of CCR3 in osteoclast formation and activity. CCR3 deficiency was associated with formation of giant hypernucleated osteoclasts, enhanced bone resorption when cultured on bone slices, and altered mRNA expression of related chemokine receptors and ligands. In addition, primary mouse calvarial osteoblasts isolated from CCR3-deficient mice showed increased mRNA expression of the osteoclast activator-related gene, receptor activator of nuclear factor kappa-B ligand, and osteoblast differentiation-associated genes. Microcomputed tomography analyses of femurs from CCR3-deficient mice revealed a bone phenotype that entailed less cortical thickness and volume. Consistent with our in vitro studies, the total number of osteoclasts did not differ between the genotypes in vivo. Moreover, an increased endocortical osteoid mineralization rate and higher trabecular and cortical bone formation rate was displayed in CCR3-deficient mice. Collectively, our data show that CCR3 deficiency influences osteoblast and osteoclast differentiation and that it is associated with thinner cortical bone in adult male mice.</p>}},
author = {{Rosendahl, Sara and Sulniute, Rima and Eklund, Michaela and Koskinen Holm, Cecilia and Johansson, Marcus J O and Kindstedt, Elin and Lindquist, Susanne and Lundberg, Pernilla}},
issn = {{1083-351X}},
keywords = {{Animals; Bone and Bones/metabolism; Cell Differentiation/physiology; Cells, Cultured; Cortical Bone/metabolism; Disease Models, Animal; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; NF-kappa B/metabolism; Osteoblasts/metabolism; Osteoclasts/metabolism; RANK Ligand/metabolism; Receptors, CCR3/deficiency; X-Ray Microtomography/methods}},
language = {{eng}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{The Journal of biological chemistry}},
title = {{CCR3 deficiency is associated with increased osteoclast activity and reduced cortical bone volume in adult male mice}},
url = {{http://dx.doi.org/10.1074/jbc.RA120.015571}},
doi = {{10.1074/jbc.RA120.015571}},
volume = {{296}},
year = {{2021}},
}