Nrf2 differentially regulates osteoclast and osteoblast differentiation for bone homeostasis.

Nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) is a master regulator of antioxidant response and protects cells from excessive oxidative stress. Nrf2 emerges as a prospective therapeutic target for metabolic bone disorders, in which the balance between osteoblastic bone formation and osteoclastic bone resorption is disrupted. However, the molecular mechanism through which Nrf2 modulates bone homeostasis remains unclear. In this study, we compared the differences in Nrf2-mediated antioxidant response and ROS regulation in osteoblasts and osteoclasts, both in vitro and in vivo. Findings indicated a close connection between the Nrf2 expression and its related antioxidant response with osteoclasts than osteoblasts. We next pharmacologically manipulated the Nrf2-mediated antioxidant response during osteoclast or osteoblast differentiation. Nrf2 inhibition enhanced osteoclastogenesis, while its activation suppressed it. In contrast, osteogenesis decreased irrespective of whether Nrf2 was inhibited or activated. These findings highlight the distinct ways in which the Nrf2-mediated antioxidant response regulates osteoclast and osteoblast differentiation, thereby contributing to the development of Nrf2 targeted therapies for metabolic bone diseases.

Microstructure, elastic deformation behavior and mechanical properties of biomedical ß-type titanium alloy thin-tube used for stents.

Cold-deformability and mechanical compatibility of the biomedical ß-type titanium alloy are the foremost considerations for their application in stents, because the lower ductility restricts the cold-forming of thin-tube and unsatisfactory mechanical performance causes a failed tissue repair. In this paper, ß-type titanium alloy (Ti-25Nb-3Zr-3Mo-2Sn, wt%) thin-tube fabricated by routine cold rolling is reported for the first time, and its elastic behavior and mechanical properties are discussed for the various microstructures. The as cold-rolled tube exhibits nonlinear elastic behavior with large recoverable strain of 2.3%. After annealing and aging, a nonlinear elasticity, considered as the intermediate stage between "double yielding" and normal linear elasticity, is attributable to a moderate precipitation of α phase. Quantitive relationships are established between volume fraction of α phase (Vα) and elastic modulus, strength as well as maximal recoverable strain (εmax-R), where the εmax-R of above 2.0% corresponds to the Vα range of 3-10%. It is considered that the "mechanical" stabilization of the (α+ß) microstructure is a possible elastic mechanism for explaining the nonlinear elastic behavior.

Open-Cellular Co-Base and Ni-Base Superalloys Fabricated by Electron Beam Melting.

Reticulated mesh samples of Co-29Cr-6Mo alloy and Ni-21Cr-9Mo-4Nb alloy (625) and stochastic foam samples of Co-29Cr-6Mo alloy fabricated by electron beam melting were characterized by optical metallography, and the dynamic stiffness (Young's modulus) was measured by resonant frequency analysis. The relative stiffness (E/Es) versus relative density (ρ/ρs) plotted on a log-log basis resulted in a fitted straight line with a slope n ≅ 2, consistent with that for ideal open cellular materials.