Proteomic profiling of human menisci from mild joint degeneration and end-stage osteoarthritis versus healthy controls

Paz-González, Rocío; Turkiewicz, Aleksandra; Ali, Neserin; Ruiz-Romero, Cristina; Blanco, Francisco J.; Englund, Martin; Önnerfjord, Patrik

doi:10.1016/j.ocarto.2023.100417

Cited by 3 publications

(1 citation statement)

References 49 publications

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“…This was further validated by qPCR validation where we report for the first time that IGFBP2 is significantly upregulated in obese synovial tissues from OA patients. Interestingly, IGFBP2 is highly abundant in both OA and RA synovial fluid [ 24 , 25 ]. IGFBPs are specifically elevated in sites of degenerated cartilage where they modulate the activity and bioavailability of IGF which is important for anabolic regulation in chondrocytes [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

Acharjee,

Wijesinghe,

Russ

et al. 2024

J Transl Med

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Background Fundamentally defined by an imbalance in energy consumption and energy expenditure, obesity is a significant risk factor of several musculoskeletal conditions including osteoarthritis (OA). High-fat diets and sedentary lifestyle leads to increased adiposity resulting in systemic inflammation due to the endocrine properties of adipose tissue producing inflammatory cytokines and adipokines. We previously showed serum levels of specific adipokines are associated with biomarkers of bone remodelling and cartilage volume loss in knee OA patients. Whilst more recently we find the metabolic consequence of obesity drives the enrichment of pro-inflammatory fibroblast subsets within joint synovial tissues in obese individuals compared to those of BMI defined ‘health weight’. As such this present study identifies obesity-associated genes in OA joint tissues which are conserved across species and conditions. Methods The study utilised 6 publicly available bulk and single-cell transcriptomic datasets from human and mice studies downloaded from Gene Expression Omnibus (GEO). Machine learning models were employed to model and statistically test datasets for conserved gene expression profiles. Identified genes were validated in OA tissues from obese and healthy weight individuals using quantitative PCR method (N = 38). Obese and healthy-weight patients were categorised by BMI > 30 and BMI between 18 and 24.9 respectively. Informed consent was obtained from all study participants who were scheduled to undergo elective arthroplasty. Results Principal component analysis (PCA) was used to investigate the variations between classes of mouse and human data which confirmed variation between obese and healthy populations. Differential gene expression analysis filtered on adjusted p-values of p < 0.05, identified differentially expressed genes (DEGs) in mouse and human datasets. DEGs were analysed further using area under curve (AUC) which identified 12 genes. Pathway enrichment analysis suggests these genes were involved in the biosynthesis and elongation of fatty acids and the transport, oxidation, and catabolic processing of lipids. qPCR validation found the majority of genes showed a tendency to be upregulated in joint tissues from obese participants. Three validated genes, IGFBP2 (p = 0.0363), DOK6 (0.0451) and CASP1 (0.0412) were found to be significantly different in obese joint tissues compared to lean-weight joint tissues. Conclusions The present study has employed machine learning models across several published obesity datasets to identify obesity-associated genes which are validated in joint tissues from OA. These results suggest obesity-associated genes are conserved across conditions and may be fundamental in accelerating disease in obese individuals. Whilst further validations and additional conditions remain to be tested in this model, identifying obesity-associated genes in this way may serve as a global aid for patient stratification giving rise to the potential of targeted therapeutic interventions in such patient subpopulations.

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Section: Discussionmentioning

confidence: 99%

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

Acharjee,

Wijesinghe,

Russ

et al. 2024

J Transl Med

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Osteoarthritis Year in Review 2024: Molecular biomarkers of osteoarthritis

Welhaven,

Welfley,

June

2025

Osteoarthritis and Cartilage

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Meniscus gene expression profiling of inner and outer zone meniscus tissue compared to cartilage and passaged monolayer meniscus cells

Fei,

Andress,

Kelly

et al. 2024

Sci Rep

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Meniscus injuries are common and while surgical strategies have improved, there is a need for alternative therapeutics to improve long-term outcomes and prevent post-traumatic osteoarthritis. Current research efforts in regenerative therapies and tissue engineering are hindered by a lack of understanding of meniscus cell biology and a poorly defined meniscus cell phenotype. This study utilized bulk RNA-sequencing to identify unique and overlapping transcriptomic profiles in cartilage, inner and outer zone meniscus tissue, and passaged inner and outer zone meniscus cells. The greatest transcriptomic differences were identified when comparing meniscus tissue to passaged monolayer cells (> 4,600 differentially expressed genes (DEGs)) and meniscus tissue to cartilage (> 3,100 DEGs). While zonal differences exist within the meniscus tissue (205 DEGs between inner and outer zone meniscus tissue), meniscus resident cells are more similar to each other than to either cartilage or passaged monolayer meniscus cells. Additionally, we identified and validated LUM, PRRX1, and SNTB1 as potential markers for meniscus tissue and ACTA2, TAGLN, SFRP2, and FSTL1 as novel markers for meniscus cell dedifferentiation. Our data contribute significantly to the current characterization of meniscus cells and provide an important foundation for future work in meniscus cell biology, regenerative medicine, and tissue engineering.

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Proteomic profiling of human menisci from mild joint degeneration and end-stage osteoarthritis versus healthy controls

Cited by 3 publications

References 49 publications

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

Osteoarthritis Year in Review 2024: Molecular biomarkers of osteoarthritis

Meniscus gene expression profiling of inner and outer zone meniscus tissue compared to cartilage and passaged monolayer meniscus cells

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