Li, JiliangSandy, BrandonDai, GuoliRoper, Randall2025-08-272025-08-272025-08https://hdl.handle.net/1805/50522https://doi.org/10.7912/S0NC-2G71IUPUIBone health is a critical element in mammalian quality of life. The Keap1/Nrf2 signaling pathway has recently been observed to be instrumental in a multitude of regulatory processes pertaining to cytoprotective gene expression, with growing evidence of its role in bone metabolism. Nrf2, activated through Keap1 deletion, is hypothesized to enhance bone quality by modulating osteoblastic, osteoclastic, and osteocytic activity. In this study, impact on bone metabolism is observed via osteoblast and osteocyte activity managed by Keap1/Nrf2 inactivation and activation respectively. Here we aimed to test if Nrf2 activation positively affects bone strength and quality by way of increased bone metabolism and as a consequence of mechanical loading. The experimental results show that osteocyte and, subsequently, osteoblast activity and operation are driven by Nrf2 actuation and reaction to the mechanical loading of bone. It is found here that the Keap1/Nrf2 pathway executes an important function in bone metabolism and increasing bone mass, strength, and quality. It is expected that this study can and will be used in further experiments of other cell types to examine the impact of the Keap1/Nrf2 pathway. Though there is more research to be performed, the Keap1/Nrf2 axis and its ability to influence bone metabolism shows promise for the potential therapeutic care and forestallment of osteoporosis in a clinical setting.en-USCC0 1.0 UniversalKeap1Nrf2Oxidative StressRedox SignalingBone BiologyOsteocytesOsteoblastsBone HomeostasisBone RemodelingThesis