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Adenosine A2A recep...
Adenosine A2A receptor null chondrocyte transcriptome resembles that of human osteoarthritic chondrocytes
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Castro, C. M. (författare)
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- Corciulo, Carmen (författare)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Friedman, B. (författare)
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Li, Z. (författare)
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Jacob, S. (författare)
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Fenyo, D. (författare)
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Cronstein, B. N. (författare)
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(creator_code:org_t)
- 2021-05-11
- 2021
- Engelska.
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Ingår i: Purinergic Signalling. - : Springer Science and Business Media LLC. - 1573-9538 .- 1573-9546. ; 17, s. 439-448
- Relaterad länk:
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https://europepmc.or...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Adenosine signaling plays a critical role in the maintenance of articular cartilage and may serve as a novel therapeutic for osteoarthritis (OA), a highly prevalent and morbid disease without effective therapeutics in the current market. Mice lacking adenosine A2A receptors (A2AR) develop spontaneous OA by 16 weeks of age, a finding relevant to human OA since loss of adenosine signaling due to diminished adenosine production (NT5E deficiency) also leads to development of OA in mice and humans. To better understand the mechanism by which A2AR and adenosine generation protect from OA development, we examined differential gene expression in neonatal chondrocytes from WT and A2AR null mice. Analysis of differentially expressed genes was analyzed by KEGG pathway analysis, and oPOSSUM and the flatiron database were used to identify transcription factor binding enrichment, and tissue-specific network analyses and patterns were compared to gene expression patterns in chondrocytes from patients with OA. There was a differential expression of 2211 genes (padj<0.05). Pathway enrichment analysis revealed that pro-inflammatory changes, increased metalloprotease, reduced matrix organization, and homeostasis are upregulated in A2AR null chondrocytes. Moreover, stress responses, including autophagy and HIF-1 signaling, seem to be important drivers of OA and bear marked resemblance to the human OA transcriptome. Although A2AR null mice are born with grossly intact articular cartilage, we identify here the molecular foundations for early-onset OA in these mice, further establishing their role as models for human disease and the potential use of adenosine as a treatment for human disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Osteoarthritis
- Chondrocyte transcriptome
- Autophagy
- Stress response
- A2AR null mouse
- articular-cartilage
- mitochondrial
- mechanisms
- senescence
- autophagy
- stress
- models
- oxygen
- cells
- cd73
- Biochemistry & Molecular Biology
- Neurosciences & Neurology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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