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Proteomic analysis of human chondrocytes under DEHP exposure

ABSTRACT: Objective: The toxicity of environmental endocrine disruptors to the reproductive and nervous systems has been widely confirmed, but the mechanism of action in bone-related diseases is still unclear. This study elucidated the molecular mechanism of the potential role of DEHP, a commonly used environmental endocrine disruptor plasticizer, in influencing the pathogenesis of knee osteoarthritis. METHODS:We extracted proteins from normal chondrocytes and chondrocytes after DEHP induction for proteomic sequencing to screen for differentially expressed proteins after DEHP induction. After this, GO and KEGG enrichment analyses were performed on the identified differentially identified proteins using bioinformatics tools. Results: DEHP exposure significantly up-regulated the expressions of phosphofructokinase (PFK), pyruvate kinase M (PKM) and lactate dehydrogenase A (LDHA) in chondrocytes, and triggered glycolytic metabolic reprogramming. The change of metabolic state further disrupts the cellular redox balance, and the level of cellular oxidative phosphorylation decreases. Conclusion: This study reveals a novel mechanism of DEHP promoting the progression of KOA through metabolic reprogramming pathway, and provides an innovative theoretical basis and practical direction for the study of the environmental etiology of KOA and the development of prevention and control strategies.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jia Sun

PROVIDER: PXD066186 | iProX | Tue Jul 15 00:00:00 BST 2025

REPOSITORIES: iProX

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Project description:Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA. Three samples of cultured chondrocytes from knee and proximal interphalangeal finger joints were compared. Gene expression of the four most differentially regulated genes was confirmed by real-time PCR in 10 independent samples.

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Proteomic analysis of human chondrocytes under DEHP exposure

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