# Targeting Parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis

## TL;DR

This study explores how cartilage metabolism changes with age and identifies a potential treatment for osteoarthritis by targeting these metabolic shifts.

## Contribution

The study reveals that Parkin regulates cartilage metabolism and shows that targeting this pathway with lauroyl-L-carnitine can ameliorate aging-related osteoarthritis.

## Key findings

- Chondrocytes shift from glycolysis to oxidative phosphorylation during aging.
- Parkin ablation reprograms cartilage metabolism and reduces osteoarthritis progression.
- Lauroyl-L-carnitine supplementation improves cartilage matrix synthesis and ameliorates OA in mice.

## Abstract

Articular cartilage degeneration may lead to osteoarthritis (OA) during the aging process, but its underlying mechanism remains unknown. Here, we found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. Parkin regulates various cellular metabolic processes. Reprogrammed cartilage metabolism by Parkin ablation decreased OXPHOS and increased glycolysis, with ameliorated aging-related OA. Metabolomics analysis indicated that lauroyl-L-carnitine (LLC) was decreased in aged cartilage, but increased in Parkin-deficient cartilage. In vitro, LLC improved the cartilage matrix synthesis of aged chondrocytes. In vivo, intra-articular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA progression. These results suggest that metabolic changes are regulated by Parkin-impaired cartilage during aging, and targeting this metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA.

•Chondrocytes exhibited energy metabolism shift during aging•Parkin regulate cartilage metabolism and the progression of aging-related OA•Targeting Parkin-regulated metabolism is a promising strategy for OA treatment

Chondrocytes exhibited energy metabolism shift during aging

Parkin regulate cartilage metabolism and the progression of aging-related OA

Targeting Parkin-regulated metabolism is a promising strategy for OA treatment

Biological sciences; Molecular biology; Metabolomics; Transcriptomics