Work

lncRNA MALAT1-mediated regulation of cholesterol-oxidative stress-iron metabolic dysregulation by paeoniflorin in osteoarthritic chondrocytes

Year: 2026

Type: article

Abstract: Context Osteoarthritis is a chronic degenerative disease characterized by metabolic dysregulation, inflammation, and oxidative stress. MALAT1 plays a key role in OA pathogenesis. Pae exhibits anti-inflammatory activity, but its regulatory role in cholesterol-oxidative stress-iron metabolism in chondrocytes remains unclear.Objective To investigate whether Pae can alleviate cholesterol-oxidative stress-iron metabolic dysregulation in OA chondrocytes via modulation of MALAT1.Materials & methods OA was induced in mice using a modified Hulth method, followed by intra-articular injection of MALAT1 overexpression plasmid. Cartilage morphology and the expression of MALAT1 and related genes/proteins were assessed by histology, RT-PCR, and Western blot. In vitro, IL-1β-treated chondrocytes were used to model OA, and MALAT1 knockdown was achieved via lentiviral transfection. FISH, RT-PCR, Western blot, and flow cytometry were used to evaluate the effects of Pae on molecular markers and apoptosis.Results In vivo In vivo, Pae improved cartilage morphology and restored the expression of key genes and proteins, whereas MALAT1 overexpression attenuated these effects. In IL-1β-treated OA chondrocytes, Pae reversed abnormal mRNA expression of MALAT1 and related genes. FISH analysis showed that Pae reduced MALAT1 fluorescence in chondrocytes. Western blot revealed that Pae significantly restored protein expression in sh-MALAT1 chondrocytes. Furthermore, flow cytometry analysis revealed that Pae intervention significantly reduced the apoptosis rate of IL-1β-induced chondrocytes from 34.57% to 27.74%. sh-MALAT1 resulted in a more pronounced reduction in chondrocyte apoptosis, with the apoptotic rate further decreasing to 13.21%.Discussion and Conclusion Paeoniflorin ameliorates cholesterol-oxidative stress-iron metabolic dysregulation in OA chondrocytes via modulation of MALAT1, providing mechanistic insight into its potential therapeutic effects.

Source: Pharmaceutical Biology

DOI: 10.1080/13880209.2026.2620862