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Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone
Paget’s Disease of Bone (PDB) is a metabolic bone disease that is characterized by dysregulated osteoclast function leading to focal abnormalities of bone remodeling. It can lead to pain, fracture, and bone deformity. G protein-coupled receptor kinase 3 (GRK3) is an important negative regulator of G...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093054/ https://www.ncbi.nlm.nih.gov/pubmed/37048054 http://dx.doi.org/10.3390/cells12070981 |
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author | Rabjohns, Emily M. Rampersad, Rishi R. Ghosh, Arin Hurst, Katlyn Eudy, Amanda M. Brozowski, Jaime M. Lee, Hyun Ho Ren, Yinshi Mirando, Anthony Gladman, Justin Bowser, Jessica L. Berg, Kathryn Wani, Sachin Ralston, Stuart H. Hilton, Matthew J. Tarrant, Teresa K. |
author_facet | Rabjohns, Emily M. Rampersad, Rishi R. Ghosh, Arin Hurst, Katlyn Eudy, Amanda M. Brozowski, Jaime M. Lee, Hyun Ho Ren, Yinshi Mirando, Anthony Gladman, Justin Bowser, Jessica L. Berg, Kathryn Wani, Sachin Ralston, Stuart H. Hilton, Matthew J. Tarrant, Teresa K. |
author_sort | Rabjohns, Emily M. |
collection | PubMed |
description | Paget’s Disease of Bone (PDB) is a metabolic bone disease that is characterized by dysregulated osteoclast function leading to focal abnormalities of bone remodeling. It can lead to pain, fracture, and bone deformity. G protein-coupled receptor kinase 3 (GRK3) is an important negative regulator of G protein-coupled receptor (GPCR) signaling. GRK3 is known to regulate GPCR function in osteoblasts and preosteoblasts, but its regulatory function in osteoclasts is not well defined. Here, we report that Grk3 expression increases during osteoclast differentiation in both human and mouse primary cells and established cell lines. We also show that aged mice deficient in Grk3 develop bone lesions similar to those seen in human PDB and other Paget’s Disease mouse models. We show that a deficiency in Grk3 expression enhances osteoclastogenesis in vitro and proliferation of hematopoietic osteoclast precursors in vivo but does not affect the osteoclast-mediated bone resorption function or cellular senescence pathway. Notably, we also observe decreased Grk3 expression in peripheral blood mononuclear cells of patients with PDB compared with age- and gender-matched healthy controls. Our data suggest that GRK3 has relevance to the regulation of osteoclast differentiation and that it may have relevance to the pathogenesis of PDB and other metabolic bone diseases associated with osteoclast activation. |
format | Online Article Text |
id | pubmed-10093054 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100930542023-04-13 Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone Rabjohns, Emily M. Rampersad, Rishi R. Ghosh, Arin Hurst, Katlyn Eudy, Amanda M. Brozowski, Jaime M. Lee, Hyun Ho Ren, Yinshi Mirando, Anthony Gladman, Justin Bowser, Jessica L. Berg, Kathryn Wani, Sachin Ralston, Stuart H. Hilton, Matthew J. Tarrant, Teresa K. Cells Article Paget’s Disease of Bone (PDB) is a metabolic bone disease that is characterized by dysregulated osteoclast function leading to focal abnormalities of bone remodeling. It can lead to pain, fracture, and bone deformity. G protein-coupled receptor kinase 3 (GRK3) is an important negative regulator of G protein-coupled receptor (GPCR) signaling. GRK3 is known to regulate GPCR function in osteoblasts and preosteoblasts, but its regulatory function in osteoclasts is not well defined. Here, we report that Grk3 expression increases during osteoclast differentiation in both human and mouse primary cells and established cell lines. We also show that aged mice deficient in Grk3 develop bone lesions similar to those seen in human PDB and other Paget’s Disease mouse models. We show that a deficiency in Grk3 expression enhances osteoclastogenesis in vitro and proliferation of hematopoietic osteoclast precursors in vivo but does not affect the osteoclast-mediated bone resorption function or cellular senescence pathway. Notably, we also observe decreased Grk3 expression in peripheral blood mononuclear cells of patients with PDB compared with age- and gender-matched healthy controls. Our data suggest that GRK3 has relevance to the regulation of osteoclast differentiation and that it may have relevance to the pathogenesis of PDB and other metabolic bone diseases associated with osteoclast activation. MDPI 2023-03-23 /pmc/articles/PMC10093054/ /pubmed/37048054 http://dx.doi.org/10.3390/cells12070981 Text en © 2023 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 Rabjohns, Emily M. Rampersad, Rishi R. Ghosh, Arin Hurst, Katlyn Eudy, Amanda M. Brozowski, Jaime M. Lee, Hyun Ho Ren, Yinshi Mirando, Anthony Gladman, Justin Bowser, Jessica L. Berg, Kathryn Wani, Sachin Ralston, Stuart H. Hilton, Matthew J. Tarrant, Teresa K. Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone |
title | Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone |
title_full | Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone |
title_fullStr | Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone |
title_full_unstemmed | Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone |
title_short | Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone |
title_sort | aged g protein-coupled receptor kinase 3 (grk3)-deficient mice exhibit enhanced osteoclastogenesis and develop bone lesions analogous to human paget’s disease of bone |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093054/ https://www.ncbi.nlm.nih.gov/pubmed/37048054 http://dx.doi.org/10.3390/cells12070981 |
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