Dataset Information

Integrated molecular phenotyping in chondrocytes identifies genes and pathways disrupted in osteoarthritis

ABSTRACT: Osteoarthritis (OA) is a degenerative joint disease with a substantial health economic burden. There is no current treatment; instead, disease management targets the main symptoms (pain and stiffness) and culminates in joint replacement surgery. OA is a disease of cartilage degeneration, but the molecular changes leading to the development of OA are still poorly understood. In this study we compare methylation, gene transcription and protein abundance at the genome-wide level in individually-matched samples of chondrocytes extracted from affected and relatively healthy articular cartilage across 12 OA patients undergoing total knee replacement. Integration analysis highlights genes that are consistently affected at multiple levels, including AQP1, CLEC3B and COL1A1, and also relevant biological pathways such as extracellular matrix organization, collagen catabolism and proteolysis. Collectively these results provide a first view of the comprehensive molecular landscape underpinning OA development and point to potential therapeutic avenues.

INSTRUMENT(S): LTQ Orbitrap Velos, Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Knee, Chondrocyte

DISEASE(S): Osteoarthritis

SUBMITTER: James Wright

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD002014 | Pride | 2018-10-24

REPOSITORIES: Pride

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			Action	DRS
	01JUL14_TMT_OA_6th_exp_RP_24-rep2.raw	Raw
	01JUL14_TMT_OA_6th_exp_RP_24.raw	Raw
	02JUL14_TMT_OA_6th_exp_RP_15.raw	Raw
	02JUL14_TMT_OA_6th_exp_RP_16.raw	Raw
	02JUL14_TMT_OA_6th_exp_RP_17.raw	Raw

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Publications

Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis.

Steinberg Julia J Ritchie Graham R S GRS Roumeliotis Theodoros I TI Jayasuriya Raveen L RL Clark Matthew J MJ Brooks Roger A RA Binch Abbie L A ALA Shah Karan M KM Coyle Rachael R Pardo Mercedes M Le Maitre Christine L CL Ramos Yolande F M YFM Nelissen Rob G H H RGHH Meulenbelt Ingrid I McCaskie Andrew W AW Choudhary Jyoti S JS Wilkinson J Mark JM Zeggini Eleftheria E

Scientific reports 20170821 1

Osteoarthritis (OA) is a common disease characterized by cartilage degeneration and joint remodeling. The underlying molecular changes underpinning disease progression are incompletely understood. We investigated genes and pathways that mark OA progression in isolated primary chondrocytes taken from paired intact versus degraded articular cartilage samples across 38 patients undergoing joint replacement surgery (discovery cohort: 12 knee OA, replication cohorts: 17 knee OA, 9 hip OA patients). W ...[more]

PMID: 28827734

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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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