Just a breath away: considerations for oxygen imbalances in osteoarthritis

Oxygen availability plays a critical role in maintaining cartilage homeostasis and influencing the progression of osteoarthritis (OA). Articular cartilage is an avascular tissue that depends on a tightly regulated hypoxic microenvironment, with oxygen gradients shaped by diffusion from synovial fluid, cartilage thickness, and mechanical loading. Both degenerative OA, which develops gradually with age, and post-traumatic osteoarthritis (PTOA), which follows joint injury and progresses more rapidly, may involve disruption of this oxygen balance. Such dysregulation, whether through reduced or elevated oxygen tension, can impair chondrocyte metabolism, increase reactive oxygen species (ROS) production, and alter hypoxia-inducible factor 1-alpha (HIF-1α) signaling, ultimately contributing to cartilage degeneration. This mini-review explores the complex oxygen dynamics in cartilage and their potential role in OA. We highlight current knowledge gaps in oxygen level assessment and mechanistic understanding, and discuss emerging therapeutic and biomaterial-based strategies, including oxygen-sensing nanoparticles, ROS-responsive scaffolds, and oxygen-generating materials, that aim to modulate the joint oxygen environment. These approaches underscore the need for temporally controlled oxygen-related pathway modulation to support cartilage repair. Advancing our understanding of oxygen regulation in joint tissues may offer new opportunities for more effective, stage-specific OA therapies.