Nuclear factor erythroid 2–related factor 2 (Nrf2) deficiency causes age-dependent progression of female osteoporosis

Nuclear factor erythroid 2–related factor 2 (Nrf2) deficiency causes age-dependent progression of female osteoporosis

Kubo, Yusuke (Medizinische Fakultat und Universitats Klinikum Aachen)
Beckmann, Rainer (Medizinische Fakultat und Universitats Klinikum Aachen)
Pahlavani, H. (TU Delft Biomaterials & Tissue Biomechanics)
Cruz Saldivar, M. (TU Delft Biomaterials & Tissue Biomechanics)
Szymanski, Katharina (Medizinische Fakultat und Universitats Klinikum Aachen)
Leeflang, M.A. (TU Delft Biomaterials & Tissue Biomechanics)
Mirzaali, Mohammad J. (TU Delft Biomaterials & Tissue Biomechanics)
Zadpoor, A.A. (TU Delft Biomaterials & Tissue Biomechanics)
Wruck, Christoph Jan (Medizinische Fakultat und Universitats Klinikum Aachen)
Jahr, H. (Medizinische Fakultat und Universitats Klinikum Aachen; Rheinisch-Westfälische Technische Hochschule)

2022

Background: Nuclear factor erythroid 2–related 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. Methods: Eighteen female wild type (WT) and 16 Nrf2-knockout (KO) mice were sacrificed at different ages (12 weeks = young mature adult and 90 weeks = old) to analyze their femurs. The morphological properties (trabecular and cortical) were evaluated by micro-computed tomography (μCT) and compared to gold standard histochemistry analysis. 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. Results: 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. Specifically, while all old WT mice showed thin metaphyseal trabeculae, trabecular bone was completely absent in 60% of old KO mice. 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. Conclusion: Our results suggest that chronic Nrf2 loss can lead to age-dependent progression of female osteoporosis.

Bone strength
Estrogen
Fracture resilience
Nrf2
Osteoporosis

http://resolver.tudelft.nl/uuid:1d11d92d-ecde-4293-b46c-fc48809b2ae3

https://doi.org/10.1186/s12891-022-05942-1

1471-2474

BMC Musculoskeletal Disorders, 23 (1)

Institutional Repository

journal article

© 2022 Yusuke Kubo, Rainer Beckmann, H. Pahlavani, M. Cruz Saldivar, Katharina Szymanski, M.A. Leeflang, Mohammad J. Mirzaali, A.A. Zadpoor, Christoph Jan Wruck, H. Jahr, More Authors