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

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.

Elasticity Approach to Predict Shape Transformation of Functionally Graded Mechanical Metamaterial under Tension.

The re-entrant structures are among the simple unit cell designs that have been widely used in the design of mechanical metamaterials. Changing the geometrical parameters of these unit cell structures, their overall elastic properties (i.e., elastic stiffness and Poisson's ratio), can be simultaneously tuned. Therefore, different design strategies (e.g., functional gradient) can be implemented to design advanced engineering materials with unusual properties. Here, using the theory of elasticity and finite element modeling, we propose a fast and direct approach to effectively design the microarchitectures of mechanical metamaterials with re-entrant structures that allow predicting complex deformation shapes under uniaxial tensile loading. We also analyze the efficiency of this method by back calculating the microarchitectural designs of mechanical metamaterials to predict the complex 1-D external contour of objects (e.g., vase and foot). The proposed approach has several applications in creating programmable mechanical metamaterials with shape matching properties for exoskeletal and soft robotic devices.