Glycolytic reprogramming impairs chondrocyte function in broilers with femoral head necrosis

TL;DR

This study shows that changes in energy metabolism in cartilage cells contribute to bone disease in chickens, suggesting targeting this process could help treat the condition.

Contribution

The study reveals glycolytic reprogramming in chondrocytes as a novel mechanism underlying femoral head necrosis in broilers.

Findings

FHN chondrocytes show increased glycolysis and reduced mitochondrial function.

Glycolytic reprogramming leads to cartilage matrix degradation in FHN broilers.

Inhibiting glycolysis reduces matrix degradation gene expression in FHN chondrocytes.

Abstract

Cartilage extracellular matrix (ECM) destruction is a hallmark of femoral head necrosis (FHN) in broilers. Chondrocytes undergo metabolic reprogramming under stress to maintain function. However, the metabolic alterations in FHN chondrocytes remain unclear. This study aims to investigate the overall changes of metabolic state in FHN chondrocytes and its functions. Femoral head cartilage of healthy and FHN broilers was collected for non-targeted metabolome and transcriptome analyses. Additionally, primary chondrocytes were isolated from femoral head cartilage of control (CON) and FHN broilers for bioenergetic analysis and mechanistic investigation. Multi-omics profiling revealed significant enrichment of the glycolysis pathway, decreased levels of tricarboxylic acid cycle metabolites (citrate and malate), upregulation of the lactate dehydrogenase A (Ldha) gene, and downregulation of genes encoding mitochondrial complexes in cartilage from FHN broilers. Compared with primary chondrocytes isolated from CON broilers, FHN primary chondrocytes exhibited elevated basal extracellular acidification rate (ECAR) and increased lactate production. Concurrently, the basal respiration of FHN chondrocytes was decreased, accompanied by unbalanced mitochondrial dynamics and decreased ATP production. Furthermore, fructose-1,6-bisphosphate (FBP) or rotenone treatment was used to mimic the metabolic shift from oxidative phosphorylation to glycolysis, resulting in downregulation of matrix synthesis genes and upregulation of matrix degradation genes in CON primary chondrocytes. Glycolysis inhibition suppressed matrix degradation gene expression in FHN chondrocytes. These findings suggest that glycolytic reprogramming occurs in FHN chondrocytes, and targeting glycolysis may alleviate ECM destruction in FHN broilers, providing a novel insight into the pathological mechanisms of FHN.

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