Reactive oxygen species on bone cells activity

Reactive oxygen species (ROS) are key players in oxidative stress, and they are generated as by-products of cellular metabolism, primarily in the mitochondria. ROS are well recognised for playing a dual role as both deleterious and beneficial species. FoxOs transcription factors are activated in oxidative stress responses and participate in the regulation of cellular functions, including cell cycle arrest, cell death, and protection from stress stimuli. FoxO activity is inhibited by growth factors and the insulin signaling pathways. They play a fundamental role in skeletal homeostasis by exerting both ROS dependent and independent effects on bone cells. FoxOs modulate osteoblastogenesis and attenuate osteoclastogenesis through both cell autonomous and indirect mechanisms. With aging there is an inevitable increment in oxidative stress that accelerates adipogenesis at the expense of osteoblastogenesis. There is also an increment in lipid oxidation to form pro-oxidant products that enhance oxidative stress generation. In addition, the estrogen withdrawal accelerates osteoclastogenesis. Given the importance of both FoxOs and ROS in aging and bone biology, understanding the cellular events and molecular pathways that are controlled by FoxOs during aging may be vital to our understanding of the regulation of age-related osteoporosis.