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

## TL;DR

This study shows that paeoniflorin can reduce harmful metabolic changes in osteoarthritic cartilage cells by targeting a specific RNA called MALAT1.

## Contribution

The novel finding is that paeoniflorin regulates cholesterol-oxidative stress-iron metabolism in osteoarthritis via MALAT1 modulation.

## Key findings

- Paeoniflorin reduced MALAT1 expression and improved cartilage morphology in osteoarthritis models.
- Paeoniflorin decreased chondrocyte apoptosis and restored key metabolic protein expression.
- MALAT1 overexpression counteracted the beneficial effects of paeoniflorin in vivo.

## Abstract

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.

To investigate whether Pae can alleviate cholesterol-oxidative stress-iron metabolic dysregulation in OA chondrocytes via modulation of MALAT1.

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.

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%.

Paeoniflorin ameliorates cholesterol-oxidative stress-iron metabolic dysregulation in OA chondrocytes via modulation of MALAT1, providing mechanistic insight into its potential therapeutic effects.