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Future investigations should give priority to dissecting the precise molecular crosstalk within the gut microbiota-ferroptosis axis and evaluating combined therapeutic strategies in preclinical models and clinical trials to validate their translational potential for OA

10.1002/jbmr.4503 J Bone Miner Res

Moreover, the hierarchical model proposed here, whereby NO functions as an upstream triggering signal and lipid peroxidation and mitochondrial ROS constitutes the downstream execution events, should not be interpreted as a strictly linear or universal sequence equally applicable to all cell types or ferroptosis inducers

These effectors, including prostaglandins, leukotrienes and thromboxanes, are produced in mammals by cyclooxygenase and lipoxygenase enzymes and act as regulators of pain, inflammation, immunity, blood pressure and reproduction

Since the mag-fura-2 assay was found to be insensitive to Mg-citrate concentration, these experiments were performed using 1 mM MgCl 2 instead of Mg-citrate