Increased NF-kB activity in osteoprogenitor-lineage cells impairs the balance of bone versus fat in the marrow of skeletally mature mice
"Senile osteoporosis" is defined as significant aging-associated bone loss, and is accompanied by increased fat in the bone marrow. The proportion of adipocytes in bone marrow is inversely correlated with bone formation, and is associated with increased risk of fracture. NF-κB is a transcription factor that functions as a master regulator of inflammation and bone remodeling. NF-κB activity increases during aging; furthermore, constitutive activation of NF-κB significantly impairs skeletal development in neonatal mice. However, the effects of NF-κB activation using a skeletally mature animal model have not been examined. In the current study, an osteoprogenitor (OP)-specific, doxycycline-regulated NF-κB activated transgenic mouse model (iNF-κB/OP) was generated to investigate the role of NF-κB in bone remodeling in skeletally mature mice. Reduced osteogenesis in the OP-lineage cells isolated from iNF-κB/OP mice was only observed in the absence of doxycycline in vitro. Bone mineral density in the metaphyseal regions of femurs and tibias was reduced in iNF-κB/OP mice. No significant differences in bone volume fraction and cortical bone thickness were observed. Osmium-stained bone marrow fat was increased in epiphyseal and metaphyseal areas in the tibias of iNF-κB/OP mice. These findings suggest that targeting NF-κB activity as a therapeutic strategy may improve bone healing and prevent aging-associated bone loss in aged patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Regenerative engineering and translational medicine - 6(2020) vom: 26. März, Seite 69-77 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lin, Tzuhua [VerfasserIn] |
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| Links: |
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| Themen: |
Bone marrow fat |
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| Anmerkungen: |
Date Revised 02.03.2021 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1007/s40883-019-00112-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM309609305 |
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| 520 | |a "Senile osteoporosis" is defined as significant aging-associated bone loss, and is accompanied by increased fat in the bone marrow. The proportion of adipocytes in bone marrow is inversely correlated with bone formation, and is associated with increased risk of fracture. NF-κB is a transcription factor that functions as a master regulator of inflammation and bone remodeling. NF-κB activity increases during aging; furthermore, constitutive activation of NF-κB significantly impairs skeletal development in neonatal mice. However, the effects of NF-κB activation using a skeletally mature animal model have not been examined. In the current study, an osteoprogenitor (OP)-specific, doxycycline-regulated NF-κB activated transgenic mouse model (iNF-κB/OP) was generated to investigate the role of NF-κB in bone remodeling in skeletally mature mice. Reduced osteogenesis in the OP-lineage cells isolated from iNF-κB/OP mice was only observed in the absence of doxycycline in vitro. Bone mineral density in the metaphyseal regions of femurs and tibias was reduced in iNF-κB/OP mice. No significant differences in bone volume fraction and cortical bone thickness were observed. Osmium-stained bone marrow fat was increased in epiphyseal and metaphyseal areas in the tibias of iNF-κB/OP mice. These findings suggest that targeting NF-κB activity as a therapeutic strategy may improve bone healing and prevent aging-associated bone loss in aged patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a NF-κB | |
| 650 | 4 | |a Senile osteoporosis | |
| 650 | 4 | |a bone marrow fat | |
| 650 | 4 | |a bone remodeling | |
| 650 | 4 | |a osteoprogenitors | |
| 700 | 1 | |a Pajarinen, Jukka |e verfasserin |4 aut | |
| 700 | 1 | |a Kohno, Yusuke |e verfasserin |4 aut | |
| 700 | 1 | |a Nabeshima, Akira |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Nathan, Karthik |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Zhenyu |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Joy Y |e verfasserin |4 aut | |
| 700 | 1 | |a Goodman, Stuart |e verfasserin |4 aut | |
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