ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2023
Adenosine A2A receptor activation reduces chondrocyte senescence.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 18 citations in OpenAlex.
- Purinergic signaling in osteoarthritis: Mechanistic insights into pathogenesis and therapeutic targeting.Genes & diseases · 2026Review
- Liposomal multimodal theranostics for bone disorders: from rational responsive delivery and biomimetic strategies to clinical translation.Journal of nanobiotechnology · 2026Review
- Intra-articular injections of liposomal adenosine improve clinical outcomes and slow radiologic progression in a preclinical canine model of osteoarthritis.Osteoarthritis and cartilage open · 2026Article
- Hybrid extracellular vesicles drive irreversible mitochondria damage and TCA metabolite deficiency-related chondrocyte senescence.Innovation (Cambridge (Mass.)) · 2026Article
- Genetic deletion of adenosine AGeroScience · 2026Article
- Adenosine and ATP differentially control osteogenic gene expression patterns in a cardiac valve cell line.Cardiology journal · 2026Article
- The molecular mechanisms and therapeutic potential of p53 in kidney injury repair: a perspective on the p53alpha/delta133p53alpha signaling axis.Renal failure · 2025Review
- Follow the Molecule from Crystal Arthropathy to Comorbidities: The 2024 G-CAN Gold Medal Award Awardee Lecture.Gout, urate, and crystal deposition disease · 2025Article
- HIF-1α Stabilization Hampers the Chondrogenic Differentiation of Aged Bone Marrow Mesenchymal Stem Cells by Adenosine AACS pharmacology & translational science · 2025Article
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- Adenosine metabolism and receptors in aging of the skin, musculoskeletal, immune and cardiovascular systems.Ageing research reviews · 2025Review
- Alternative Splicing: Emerging Roles in Anti-Aging Strategies.Biomolecules · 2025Review
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
- Get Spliced: Uniting Alternative Splicing and Arthritis.International journal of molecular sciences · 2024Review
- Genetic Polymorphisms of P2RX7 but Not of ADORA2A Are Associated with the Severity of SARS-CoV-2 Infection.International journal of molecular sciences · 2024Article
- Purines and Adenosine Receptors in Osteoarthritis.Biomolecules · 2023Review
- Pharmacology of Adenosine Receptors: Recent Advancements.Biomolecules · 2023Review
- Adenosine A2A receptor activation reduces chondrocyte senescence.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Biomaterial-Based Gene Delivery: Advanced Tools for Enhanced Cartilage Regeneration.Drug design, development and therapy · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Osteoarthritis (OA) pathogenesis is associated with reduced chondrocyte homeostasis and increased levels of cartilage cellular senescence. Chondrosenescence is the development of cartilage senescence that increases with aging joints and disrupts chondrocyte homeostasis and is associated with OA. Adenosine A2A receptor (A2AR) activation in cartilage via intra-articular injection of liposomal A2AR agonist, liposomal-CGS21680, leads to cartilage regeneration in vivo and chondrocyte homeostasis. A2AR knockout mice develop early OA isolated chondrocytes demonstrate upregulated expression of cellular senescence and aging-associated genes. Based on these observations, we hypothesized that A2AR activation would ameliorate cartilage senescence. We found that A2AR stimulation of chondrocytes reduced beta-galactosidase staining and regulated levels and cell localization of common senescence mediators p21 and p16 in vitro in the human TC28a2 chondrocyte cell line. In vivo analysis similarly showed A2AR activation reduced nuclear p21 and p16 in obesity-induced OA mice injected with liposomal-CGS21680 and increased nuclear p21 and p16 in A2AR knockout mouse chondrocytes compared to wild-type mice. A2AR agonism also increased activity of the chondrocyte Sirt1/AMPK energy-sensing pathway by enhancing nuclear Sirt1 localization and upregulating T172-phosphorylated (active) AMPK protein levels. Lastly, A2AR activation in TC28a2 and primary human chondrocytes reduced wild-type p53 and concomitantly increased p53 alternative splicing leading to increase in an anti-senescent p53 variant, Δ133p53α. The results reported here indicate that A2AR signaling promotes chondrocyte homeostasis in vitro and reduces OA cartilage development in vivo by reducing chondrocyte senescence.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.