An inducible explant model of osteoclast-osteoprogenitor coordination in exacerbated osteoclastogenesis
Summary: Elucidating a basic blueprint of osteoclast-osteoblast coordination in skeletal remodeling and understanding how this coordination breaks down with age and disease is essential for addressing the growing skeletal health problem in our aging population. The paucity of simple, activatable, bi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223005473 |
| _version_ | 1797851292611117056 |
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| author | Jarred M. Whitlock Luis F. de Castro Michael T. Collins Leonid V. Chernomordik Alison M. Boyce |
| author_facet | Jarred M. Whitlock Luis F. de Castro Michael T. Collins Leonid V. Chernomordik Alison M. Boyce |
| author_sort | Jarred M. Whitlock |
| collection | DOAJ |
| description | Summary: Elucidating a basic blueprint of osteoclast-osteoblast coordination in skeletal remodeling and understanding how this coordination breaks down with age and disease is essential for addressing the growing skeletal health problem in our aging population. The paucity of simple, activatable, biologically relevant models of osteoclast-osteoblast coordination has hindered our understanding of how skeletal remolding is regulated. Here, we describe an inducible ex vivo model of osteoclast-osteoblast progenitor coordination. Induction activates the release of osteoclastogenic factors from osteoprogenitors, which elicits the differentiation and fusion of neighboring preosteoclasts. In turn, multinucleated osteoclasts release soluble coupling factors, RANK+ extracellular vesicles and promote osteoprogenitor proliferation, recapitulating aspects of perturbed coordination in diseases underpinned by excessive osteoclast formation. We expect this model to expedite the investigation of cell-cell fusion, osteoclast-osteoblast progenitor coordination, and extracellular vesicle signaling during bone remodeling and offer a powerful tool for evaluating signaling cascades and novel therapeutic interventions in osteoclast-linked skeletal disease. |
| first_indexed | 2024-04-09T19:14:26Z |
| format | Article |
| id | doaj.art-41e47cbf2475412a8a4b8000d9ae1202 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T19:14:26Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-41e47cbf2475412a8a4b8000d9ae12022023-04-06T06:12:53ZengElsevieriScience2589-00422023-04-01264106470An inducible explant model of osteoclast-osteoprogenitor coordination in exacerbated osteoclastogenesisJarred M. Whitlock0Luis F. de Castro1Michael T. Collins2Leonid V. Chernomordik3Alison M. Boyce4Section on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding authorSkeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD20892, USASkeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD20892, USASection on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USAMetabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD20892, USASummary: Elucidating a basic blueprint of osteoclast-osteoblast coordination in skeletal remodeling and understanding how this coordination breaks down with age and disease is essential for addressing the growing skeletal health problem in our aging population. The paucity of simple, activatable, biologically relevant models of osteoclast-osteoblast coordination has hindered our understanding of how skeletal remolding is regulated. Here, we describe an inducible ex vivo model of osteoclast-osteoblast progenitor coordination. Induction activates the release of osteoclastogenic factors from osteoprogenitors, which elicits the differentiation and fusion of neighboring preosteoclasts. In turn, multinucleated osteoclasts release soluble coupling factors, RANK+ extracellular vesicles and promote osteoprogenitor proliferation, recapitulating aspects of perturbed coordination in diseases underpinned by excessive osteoclast formation. We expect this model to expedite the investigation of cell-cell fusion, osteoclast-osteoblast progenitor coordination, and extracellular vesicle signaling during bone remodeling and offer a powerful tool for evaluating signaling cascades and novel therapeutic interventions in osteoclast-linked skeletal disease.http://www.sciencedirect.com/science/article/pii/S2589004223005473Biological sciencesCell biologyStem cells research |
| spellingShingle | Jarred M. Whitlock Luis F. de Castro Michael T. Collins Leonid V. Chernomordik Alison M. Boyce An inducible explant model of osteoclast-osteoprogenitor coordination in exacerbated osteoclastogenesis iScience Biological sciences Cell biology Stem cells research |
| title | An inducible explant model of osteoclast-osteoprogenitor coordination in exacerbated osteoclastogenesis |
| title_full | An inducible explant model of osteoclast-osteoprogenitor coordination in exacerbated osteoclastogenesis |
| title_fullStr | An inducible explant model of osteoclast-osteoprogenitor coordination in exacerbated osteoclastogenesis |
| title_full_unstemmed | An inducible explant model of osteoclast-osteoprogenitor coordination in exacerbated osteoclastogenesis |
| title_short | An inducible explant model of osteoclast-osteoprogenitor coordination in exacerbated osteoclastogenesis |
| title_sort | inducible explant model of osteoclast osteoprogenitor coordination in exacerbated osteoclastogenesis |
| topic | Biological sciences Cell biology Stem cells research |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223005473 |
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