Chronic Nrf2 deficiency affects age- and gender- dependent bone and cartilage acquisition in murine femur

Introduction Nuclear factor erythroid 2–related factor 2 (Nrf2) is crucial for maintaining cellular redox homeostasis and it also affects bone and cartilage metabolism. However, its age- and gender- dependent influence has yet to be described. The aim of this study was to investigate the role of Nrf2 on bone and cartilage acquisition in young and elderly mice by using a micro-computed tomography (µCT).

Methods Twenty-eight wild type (WT) (female: 17, male: 11) and 18 Nrf2-knockout (KO) (female: 12, male: 6) mice were used for this study. Mice were sacrificed at different points in time; young age at 3 months of age and older age at 20 months of age. Femur length, trabecular parameters [thickness (Tb.Th) and bone mineral density (BMD)], cortical parameters [thickness (Ct. Th) and area (Ct.Ar)], and height of non-calcified zone (NCZ) in growth plate (only in young mice) were measured by scanning extracted femurs using µCT.

Results The femur length in older WT mice was significantly longer than younger WT mice in both female and male, while there was no significant difference between young and older KO mice. The Tb.Th, BMD, Ct.Th, and Ct.Ar in older KO mice were significantly lower than older WT mice in female, while there was no significant difference between young WT and KO mice in female and between young/older WT and KO mice in male. No trabecular bone was observed in 75 % of older KO mice regardless of the presence of thin trabecular bone in all older WT mice (Figure A). The NCZ in growth plate in KO mice was significantly lower than WT mice in female despite no significant difference in male. Early growth plate disclosure was observed in 43 % of female KO mice regardless of the presence of growth plate in all WT mice (Figure B).

Discussion In this study, 20-month-old female KO mice had lower trabecular and cortical bone quantity compared with WT mice regardless of no significant difference in 3-month-old. Additionally, 3-month-old female KO mice had reduced cartilage layer in growth plate and early growth plate closure. Considering that these findings were not observed in male mice, these results suggest that chronic Nrf2 deficiency can affect bone and cartilage acquisition especially in female and lead to severe osteoporotic change in elderly female.

Keywords Nrf2,bone, cartilage, growth plate, osteoporosis

Korrespondenzadresse Abraham Jesus Herrera, Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany

E-Mail [e-mail]

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Publikationsverlauf

Artikel online veröffentlicht:
05. März 2021