Intraarticular injection of liposomal adenosine reduces cartilage damage in established murine and rat models of osteoarthritis
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ABSTRACT:
PROVIDER: PRJNA612020 | ENA |
REPOSITORIES: ENA
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Project description:Osteoarthritis (OA) affects nearly 10% of the population of the United States and other industrialized countries and, at present, short of surgical joint replacement, there is no therapy available that can reverse the progression of the disease OA. Adenosine, acting at its A2A receptor (A2AR), is a critical autocrine factor for maintenance of cartilage homeostasis. Here we report that injection of liposomal suspensions of a selective A2AR agonist, CGS21680, significantly reduced OA cartilage damage in a rat model of established post-traumatic OA (PTOA). Differential expression analysis of mRNA from chondrocytes harvested from knees of rats with PTOA treated with liposomal A2AR agonist revealed downregulation of genes associated with matrix degradation and upregulation of genes associated with cell proliferation as compared to liposomes alone.
2020-09-01 | GSE146813 | GEO
Project description: Not available
| S-EPMC7418027 | biostudies-literature
Project description:Osteoarthritis is characterized by cartilage destruction, chronic inflammation, and subchondral sclerosis. Evidence showed that nuclear receptor family is closely associated with cartilage damage in an unclear molecular mechanism. Here, we investigated the role and molecular mechanism of the retinoic acid receptor-related orphan receptor-α (RORα), an important member of nuclear receptor, in regulating cartilage degradation and osteoarthritis pathogenesis. Investigation to osteoarthritis clinical specimen showed that the degree of RORα elevation is positively correlated with the severity of osteoarthritis and cartilage damage. In an in vivo osteoarthritis models induced by anterior crucial ligament transaction, intraarticularly injection of siRora adenovirus reversed the cartilage damage. RORα knock-down increased the protein expression level of anabolic factor such as type II collagen, Aggrecan, and decreased the expression of catabolic factor. RNA-seq data suggested IL-6/STAT3 pathway is significantly down-regulated. Mechanistically, RORα knock-down decreased the expression level of both IL-6 and phosphorylated STAT3. RORα exerted its effect on IL-6/STAT3 signaling in two different ways, which includes interaction with STAT3 and IL6 promoter. Taken together, our findings indicated the pivotal role of RORα/IL-6/STAT3 axis in osteoarthritis progression and confirmed RORα knock-down exerted therapeutic effect in human chondrocyte thus providing a potential drug target in osteoarthritis therapy.
2021-04-20 | GSE172291 | GEO
Project description:HPIP controls osteoarthritis cartilage degeneration
| PRJNA391300 | ENA
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: Not available
| S-EPMC5437286 | biostudies-literature
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:ASS lime injection - injection site
| PRJEB6137 | ENA
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: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