Osteoblast-Specific Overexpression of Nucleolar Protein NO66/RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult Mice
In previous study, we showed that nucleolar protein 66 (NO66) is a chromatin modifier and negatively regulates Osterix activity as well as mesenchymal progenitor differentiation. Genetic ablation of the NO66 (RIOX1) gene in cells of the Prx1-expressing mesenchymal lineage leads to acceleration of os...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Hindawi Limited
2023-01-01
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| Series: | Journal of Osteoporosis |
| Online Access: | http://dx.doi.org/10.1155/2023/8998556 |
| _version_ | 1797945525690957824 |
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| author | Qin Chen Krishna M. Sinha Benoit de Crombrugghe Ralf Krahe |
| author_facet | Qin Chen Krishna M. Sinha Benoit de Crombrugghe Ralf Krahe |
| author_sort | Qin Chen |
| collection | DOAJ |
| description | In previous study, we showed that nucleolar protein 66 (NO66) is a chromatin modifier and negatively regulates Osterix activity as well as mesenchymal progenitor differentiation. Genetic ablation of the NO66 (RIOX1) gene in cells of the Prx1-expressing mesenchymal lineage leads to acceleration of osteochondrogenic differentiation and a larger skeleton in adult mice, whereas mesenchyme-specific overexpression of NO66 inhibits osteochondrogenesis resulting in dwarfism and osteopenia. However, the impact of NO66 overexpression in cells of the osteoblast lineage in vivo remains largely undefined. Here, we generated osteoblast-specific transgenic mice overexpressing a FLAG-tagged NO66 transgene driven by the 2.3 kB alpha-1type I collagen (Col1a1) promoter. We found that overexpression of NO66 in cells of the osteoblast lineage did not cause overt defects in developmental bones but led to osteoporosis in the long bones of adult mice. This includes decreased bone volume (BV), bone volume density (bone volume/total volume, BV/TV), and bone mineral density (BMD) in cancellous compartment of long bones, along with the accumulation of fatty droplets in bone marrow. Ex vivo culture of the bone marrow mesenchymal stem/stromal cells (BMSCs) from adult Col1a1-NO66 transgenic mice showed an increase in adipogenesis and a decrease in osteogenesis. Taken together, these data demonstrate a crucial role for NO66 in adult bone formation and homeostasis. Our Col1a1-NO66 transgenic mice provide a novel animal model for the mechanistic and therapeutic study of NO66 in osteoporosis. |
| first_indexed | 2024-04-10T20:57:31Z |
| format | Article |
| id | doaj.art-37fd898b717f4d80b836f9001cba744b |
| institution | Directory Open Access Journal |
| issn | 2042-0064 |
| language | English |
| last_indexed | 2024-04-10T20:57:31Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Journal of Osteoporosis |
| spelling | doaj.art-37fd898b717f4d80b836f9001cba744b2023-01-23T00:56:04ZengHindawi LimitedJournal of Osteoporosis2042-00642023-01-01202310.1155/2023/8998556Osteoblast-Specific Overexpression of Nucleolar Protein NO66/RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult MiceQin Chen0Krishna M. Sinha1Benoit de Crombrugghe2Ralf Krahe3Department of Epigenetics and Molecular CarcinogenesisDepartment of GeneticsDepartment of GeneticsDepartment of GeneticsIn previous study, we showed that nucleolar protein 66 (NO66) is a chromatin modifier and negatively regulates Osterix activity as well as mesenchymal progenitor differentiation. Genetic ablation of the NO66 (RIOX1) gene in cells of the Prx1-expressing mesenchymal lineage leads to acceleration of osteochondrogenic differentiation and a larger skeleton in adult mice, whereas mesenchyme-specific overexpression of NO66 inhibits osteochondrogenesis resulting in dwarfism and osteopenia. However, the impact of NO66 overexpression in cells of the osteoblast lineage in vivo remains largely undefined. Here, we generated osteoblast-specific transgenic mice overexpressing a FLAG-tagged NO66 transgene driven by the 2.3 kB alpha-1type I collagen (Col1a1) promoter. We found that overexpression of NO66 in cells of the osteoblast lineage did not cause overt defects in developmental bones but led to osteoporosis in the long bones of adult mice. This includes decreased bone volume (BV), bone volume density (bone volume/total volume, BV/TV), and bone mineral density (BMD) in cancellous compartment of long bones, along with the accumulation of fatty droplets in bone marrow. Ex vivo culture of the bone marrow mesenchymal stem/stromal cells (BMSCs) from adult Col1a1-NO66 transgenic mice showed an increase in adipogenesis and a decrease in osteogenesis. Taken together, these data demonstrate a crucial role for NO66 in adult bone formation and homeostasis. Our Col1a1-NO66 transgenic mice provide a novel animal model for the mechanistic and therapeutic study of NO66 in osteoporosis.http://dx.doi.org/10.1155/2023/8998556 |
| spellingShingle | Qin Chen Krishna M. Sinha Benoit de Crombrugghe Ralf Krahe Osteoblast-Specific Overexpression of Nucleolar Protein NO66/RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult Mice Journal of Osteoporosis |
| title | Osteoblast-Specific Overexpression of Nucleolar Protein NO66/RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult Mice |
| title_full | Osteoblast-Specific Overexpression of Nucleolar Protein NO66/RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult Mice |
| title_fullStr | Osteoblast-Specific Overexpression of Nucleolar Protein NO66/RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult Mice |
| title_full_unstemmed | Osteoblast-Specific Overexpression of Nucleolar Protein NO66/RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult Mice |
| title_short | Osteoblast-Specific Overexpression of Nucleolar Protein NO66/RIOX1 in Mouse Embryos Leads to Osteoporosis in Adult Mice |
| title_sort | osteoblast specific overexpression of nucleolar protein no66 riox1 in mouse embryos leads to osteoporosis in adult mice |
| url | http://dx.doi.org/10.1155/2023/8998556 |
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