| First Author | Lin T | Year | 2020 |
| Journal | Regen Eng Transl Med | Volume | 6 |
| Pages | 69-77 | PubMed ID | 32377560 |
| Mgi Jnum | J:376226 | Mgi Id | MGI:8269055 |
| Doi | 10.1007/s40883-019-00112-7 | Citation | Lin T, et al. (2020) Increased NF-kB activity in osteoprogenitor-lineage cells impairs the balance of bone versus fat in the marrow of skeletally mature mice. Regen Eng Transl Med 6:69-77 |
| abstractText | "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-kappaB is a transcription factor that functions as a master regulator of inflammation and bone remodeling. NF-kappaB activity increases during aging; furthermore, constitutive activation of NF-kappaB significantly impairs skeletal development in neonatal mice. However, the effects of NF-kappaB activation using a skeletally mature animal model have not been examined. In the current study, an osteoprogenitor (OP)-specific, doxycycline-regulated NF-kappaB activated transgenic mouse model (iNF-kappaB/OP) was generated to investigate the role of NF-kappaB in bone remodeling in skeletally mature mice. Reduced osteogenesis in the OP-lineage cells isolated from iNF-kappaB/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-kappaB/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-kappaB/OP mice. These findings suggest that targeting NF-kappaB activity as a therapeutic strategy may improve bone healing and prevent aging-associated bone loss in aged patients. |
