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Nuclear factor erythroid 2βrelated factor 2 Nrf2 is a crucial transcription factor for cellular redox homeostasis. The association of Nrf2 with elderly female osteoporotic has yet to be fully described. The aim was to elucidate a potential age-dependent Nrf2 contribution to female osteoporosis in mice. The quasi-static compression tests were performed to calculate the mechanical properties of bones.
Additionally, the population of bone resorbing cells and aromatase expression by osteocytes was immunohistochemically evaluated and empty osteocyte lacunae was counted in cortical bone. Old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density BMD , cortical thickness, cortical area, and bone fraction compared to old WT mice, regardless of no significant difference in skeletally mature young adult mice between WT and KO.
Additionally, old KO mice showed significantly more osteoclast-like cells and fewer aromatase-positive osteocytes than WT mice, whereas the occurrence of empty osteocyte lacunae did not differ between both groups. Nrf2-KO mice further showed an age-dependently reduced fracture resilience compared to age-matched WT mice. Our results suggest that chronic Nrf2 loss can lead to age-dependent progression of female osteoporosis. The association between Nrf2 and osteoporosis has not been elucidated.
These suggest Nrf2 deficiency may result in osteoporosis. It generally affects bone turnover through reducing osteoblastogenesis but increasing osteoclastogenesis, leading to a net decrease in bone mass, a condition known as osteoporosis [ 2 , 3 ]. Additionally, intrinsic oxidative stress can cause delayed fracture healing or nonunion fractures due to the irreversible cell damage by excessive toxic radicals [ 4 , 5 ].