αKlotho and sTGFBR2 treatment promotes endogenous cartilage regeneration and prevents osteoarthritis progression
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE118559 | GEO | 2020/01/22
REPOSITORIES: GEO
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Project description:Articular cartilage is deprived of blood vessels and nerves, and the only cells residing in this tissue are chondrocytes. The molecular properties of the articular cartilage and the architecture of the extracellular matrix demonstrate a complex structure that differentiates on the depth of tissue. Osteoarthritis (OA) is a degenerative joint disease, the most common form of arthritis, affecting the whole joint. It is associated with ageing and affects the joints that have been continually stressed throughout life including the knees, hips, fingers, and lower spine region. OA is a multifactorial condition of joint characterised by articular cartilage loss, subchondral bone sclerosis, and inflammation leading to progressive joint degradation, structural alterations, loss of mobility and pain. Articular cartilage biology is well studied with a focus on musculoskeletal diseases and cartilage development. However, there are relatively few studies focusing on zonal changes in the cartilage during osteoarthritis.
2022-05-19 | PXD029116 | Pride
Project description:Osteoarthritis (OA) is an age-related degenerative musculoskeletal disease characterised by loss of articular cartilage, synovitis, abnormal bone proliferation and subchondral bone sclerosis. Underlying OA pathogenesis is yet to be fully elucidated with no OA specific biomarkers in clinical use. Ex-vivo equine cartilage explants (n=5) were incubated in TNF-α/IL-1β supplemented culture media for 8 days, with media removed and replaced at 2, 5 and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent 1D 1H nuclear magnetic resonance metabolomic analysis with media samples also undergoing mass spectrometry proteomic analysis. Within the cartilage, metabolites glucose and lysine were elevated following TNF-α/IL-1β treatment whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine levels decreased. Within the culture media, four, four and six differentially abundant metabolites and 154, 138 and 72 differentially abundant proteins, with > 2 fold change, were identified for 1-2 day, 3-5 day and 6-8 day time points respectively. Nine potential novel OA neopeptides were elevated in treated media. Our novel study identified metabolites, proteins and extracellular matrix derived neopeptides which provides insightful information on OA pathogenesis, enabling potential translation for clinical markers and possible novel therapeutic targets.
2020-09-30 | MTBLS1495 | MetaboLights
Project description:Osteoarthritis causes pain and functional disability for over 500 million people worldwide and characterized by progressive loss of cartilage from the articulating surfaces of diarthrodial joints. Although the etiology of the disease is unknown, it is widely accepted that these degenerative changes arise from an imbalance of synthetic and degradative pathways that control cartilage extracellular matrix metabolism. Genome-wide U133A Affymetrix oligonucleotide array set was used to comprehensively investigate the expression pattern in non-osteoarthritis (normal) and cartilage obtained from OA patients undergoing knee replacement surgery. This study was undertaken to better understand the molecular basis of the disease and to provide relevant insight into phenotypical alterations and mechanisms involved in OA pathogenesis.
2021-03-18 | GSE169077 | GEO
Project description:Osteoarthritis (OA) is the most prevalent joint disease with the typifying feature being the progressive degradation of articular cartilage during disease progression. In this study we used whole transcriptome RNA-seq as a tool to compare gene expression changes between age-matched osteoarthritic human hip OA cartilage (n=10) compared to control (neck of femur fracture) cartilage (n=6) [GSE107308]. All cartilage was from patients undergoing acetabulofemoral joint replacement. Cartilage RNA was isolated from cartilage within 2 hr of joint replacement surgery, mRNA was polyA purified and transcript expression was analysed using 78-base paired-end sequencing generating on average 28 million reads/sample sequencing. The data shows excellent correlation with our previous microarray data but identifies significantly more differentially expressed transcripts plus novel transcript variants, several of which have been validated by real-time qPCR. Our work sheds further light on chondrocyte transcriptome expression and highlights gene expression changes and novel transcripts potentially important in osteoarthritis progression
2019-03-01 | GSE111357 | GEO
Project description:Osteoarthritis (OA) is an age-related degenerative musculoskeletal disease characterised by loss of articular cartilage, synovitis, abnormal bone proliferation and subchondral bone sclerosis. The underlying pathogenesis of OA is yet to be fully elucidated with no OA specific biomarkers in clinical use. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) allow identification of the global metabolome and proteome respectively. During this study, ex-vivo equine cartilage explants (n=5) were incubated in TNF-α/IL-1β supplemented culture media for 8 days, with media removed and replaced at 2, 5 and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent 1H NMR metabolic analysis with media samples also undergoing MS proteomic analysis. Within the cartilage, metabolites glucose and lysine were elevated following TNF-α/IL-1β treatment whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine levels decreased. Within the culture media, four, four and six metabolites were identified as being differentially abundant between control and treatment groups for 1-2 day, 3-5 day and 6-8 day time points respectively. Culture media proteomics identified 154, 138 and 72 proteins differentially abundant, with > 2 fold change, between control and treatment groups for 1-2 day, 3-5 day and 6-8 day time points respectively. Nine potential novel OA neopeptides were elevated in treated media. This is the first study to use a multi ‘omics’ approach to simultaneously investigate the metabolomic profile of ex-vivo cartilage and metabolomic/proteomic profiles of culture media using the TNF-α/IL-1β ex-vivo OA cartilage model. This study has identified a panel of metabolites, proteins and extracellular matrix derived neopeptides which are differentially abundant during an early phase of the OA model which may provide further information on underlying disease pathogenesis, allow potential translation for clinical markers and possible novel therapeutic targets.
2020-08-03 | PXD017153 | Pride
Project description:Cartilage mineralization is a tightly controlled process, imperative for skeletal growth and fracture repair. However, in osteoarthritis (OA), cartilage mineralization may impact the joint range of motion, inflict pain and may increase chances for joint effusion. Here we attempt to understand the link between inflammation and cartilage mineralization by targeting SIRT1 and LEF1, both reported to have contrasting effects on cartilage.
2022-05-16 | GSE200522 | GEO
Project description:Articular cartilage degeneration, which may lead to osteoarthritis (OA), is a normal component of the aging process, but its underlying mechanism remains unknown. We found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. 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 OA chondrocytes. In vivo, intraarticular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA. These results suggest that metabolic changes are regulated by parkin-impaired cartilage during aging, and targeting the metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA.
2024-06-18 | GSE249510 | GEO
Project description:Articular cartilage degeneration, which may lead to osteoarthritis (OA), is a normal component of the aging process, but its underlying mechanism remains unknown. We found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. 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 OA chondrocytes. In vivo, intraarticular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA. These results suggest that metabolic changes are regulated by parkin-impaired cartilage during aging, and targeting the metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA.
2024-06-18 | GSE249509 | GEO
Project description:Objective: To assess the impact of osteoarthritis (OA) on the transcripts and biological process in the articular cartilage between patients with and without OA. Design: Patients undergoing arthroscopic partial meniscectomy (APM) without any evidence for OA and patients undergoing total knee arthroplasty (TKA) due to end-stage OA were consented. Healthy-appearing cartilage was garnered from the non-weight bearing site of the medial intercondylar notch. RNA preparation was subjected to SurePrint G3 human 8X60K RNA microarrays to probe differentially expressed (DE) transcripts followed by computational exploration of underlying biological processes and pathways. Real-time PCR was performed on selected transcripts to validate microarrays data. Results: We identified 603 transcripts significantly (FDR <0.05) differentially expressed (293 elevated, 310 repressed) between APM and TKA samples (1.5 fold). Among these, CFD, CSN1S1, TSPAN11, CSF1R and CD14 were the most prominent transcripts elevated in TKA group, CHI3L2, MEG3, HILPDA, COL3A1, COL27A and FGF2 were most highly repressed in TKA samples. Few long intergenic non-coding RNAs (linRNAs), and small nuclear RNAs (snoRNAs) were also differentially expressed between the two groups. Conclusions: Numerous transcripts with potential relevance to the pathogenesis of OA are DE in OA and non-OA cartilage. These data suggest an involvement of metabolic signaling and epigenetic markers (lincRNAs, snoRNAs) in cartilage.
2018-08-02 | GSE117999 | GEO
Project description:Osteoarthritis (OA) is a joint condition associated with articular cartilage loss, low-grade synovitis and alterations in subchondral bone and periarticular tissues. In OA, the interest for mesenchymal stem cell (MSC)-EV therapeutic applications has increased. We have assessed the immunomodulary properties of adipose-derived MSCs (AD-MSCs) microvesicles (MV) and exosomes (EX) in interleukin (IL)-1β stimulated OA chondrocytes and cartilage explants and characterized them by mass spectrometry in order to uncover novel mediators in (AD-MSC)-EV immunomodulation.
2022-02-23 | PXD009077 | Pride