Abstract
Oxidative stress plays a central role in physiological and pathological bone conditions. Its role in signalment and control of bone cell population differentiation, activity, and fate is increasingly recognized. The possibilities of its use and manipulation with therapeutic goals are virtually unending. However, how redox balance interplays with the response to mechanical stimuli is yet to be fully understood. The present work summarizes current knowledge on these aspects, in an integrative and broad introductory perspective.
Highlights
Oxidative stress plays an important role in homeostasis and disease in most tissues
Hypoxia induces bone morphogenetic protein 2 (BMP2) expression by mesenchymal stem cells through a pathway independent from hypoxia inducible factor (HIF)-1; BMP2 is a powerful inductor of osteo and chondrogenesis, and its induction happens through a redox-sensitive mechanism; if hypoxia is prevented, BMP2 secretion is inhibited and healing is impaired, as happens in fracture non-union (Muinos-López et al, 2016)
NOSknockout mice show impaired fracture healing, through deregulation of arginine-nitric oxide (NO) metabolism, paired with increased neutrophil influx to the fracture site; this study focused on the activity of NOS2 and NOS3, not of NOS1, the most relevant for the latter remodeling phase (Meesters et al, 2016)
Summary
Oxidative stress plays an important role in homeostasis and disease in most tissues. Reactive species are continuously generated as byproducts of normal cellular metabolism. Antioxidant mechanisms, acting via specific scavenger reactions and detoxification pathways, revert its accumulation and avoid oxidative stress-related damage (Reis et al, 2021). When oxidative stress remains because of an imbalance between the production and scavenging of reactive species, it results in an array of physiopathologic changes, consequence of a spiral of new sources of free radicals and oxidative species and increased damage (Reis et al, 2021). Oxidative eustress or physiological oxidative stress is positive and a fundamental signal and control mechanism (Sies et al, 2017); low concentrations of ROS and RNS allow reversible oxidative/nitrosative modifications of redoxsensitive residues in regulatory proteins; these modifications may translate into a loss or gain of function or a change of function (Dröge, 2002; Moldogazieva et al, 2018). Oxidative distress is associated with high burden, supraphysiological oxidative challenge and has deleterious consequences, leading to oxidative damage of biomolecules and disruption of the redox signaling pathways (Sies, 2019)
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