{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nDexamethasone (DEX) treatment in human osteoblasts induces oxidative stress and cell apoptosis, processes that can be alleviated by activation of the Nrf2 signaling cascade. Recent studies identified microRNA-4523 (miR-4523) as a novel regulator targeting phosphoglycerate kinase 1 (PGK1), a key enzyme that normally suppresses Nrf2 activity. miR-4523 binds directly to the 3′ untranslated region (UTR) of PGK1 mRNA, thereby reducing its expression and initiating downstream activation of the Nrf2 pathway. This activation involves disruption of the Keap1–Nrf2 complex, stabilization of Nrf2 protein, its nuclear translocation, and enhanced transcription of antioxidant genes like NQO1, GCLC, and HO1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nExperimental overexpression of miR-4523 in human osteoblasts, achieved via lentiviral constructs, significantly reduced PGK1 expression and activated the Nrf2 cascade, leading to a notable decrease in DEX-induced reactive oxygen species production, cellular oxidative injury, and apoptosis. In contrast, when Nrf2 was silenced or genetically deleted, the cytoprotective effects of miR-4523 overexpression were abrogated, confirming that the protective mechanism is at least partly mediated by Nrf2 activation. Moreover, experiments utilizing a PGK1 construct lacking the 3′-UTR confirmed that the miR-4523 effect was specifically mediated through PGK1 targeting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, clinically relevant observations have revealed that miR-4523 is downregulated in necrotic femoral head tissues from patients receiving DEX, suggesting a pathophysiological relevance of the miR-4523–PGK1–Nrf2 axis in bone health. Overall, miR-4523 functions as an important endogenous modulator that protects osteoblasts from glucocorticoid-induced oxidative damage by silencing PGK1 and consequently enhancing Nrf2-mediated antioxidant responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jin-Qian Liang, Zhen-Tao Zhou, Lin Bo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphoglycerate kinase 1 silencing by a novel microRNA microRNA-4523 protects human osteoblasts from dexamethasone through activation of Nrf2 signaling cascade."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-04250-1"}], "href": "https://doi.org/10.1038/s41419-021-04250-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34667156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34667156"}]}]}]}