Effects of an adenosine kinase inhibitor and an adenosine deaminase inhibitor on accumulation of extracellular adenosine by equine articular chondrocytes.
Abstract: To investigate accumulation of extracellular adenosine (ADO) by equine articular chondrocytes and to compare effects of adenosine kinase inhibition and adenosine deaminase inhibition on the amount of nitric oxide (NO) produced by lipopolysaccharide (LPS)-stimulated chondrocytes. Methods: Articular cartilage from metacarpophalangeal and metatarsophalangeal joints of 14 horses. Methods: Chondrocytes were cultured as monolayers, and cells were incubated with LPS, the adenosine kinase inhibitor 5'-iodotubercidin (ITU), or the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA). Concentrations of ADO in cell supernatants were measured by use of reverse-phase high-performance liquid chromatography. Effect of inhibition of enzymatic metabolism of ADO on induced NO production was evaluated by exposing cells to a combination of LPS and ITU or LPS and EHNA. Results: Articular chondrocytes accumulated extracellular ADO when exposed to LPS or ITU. Chondrocytes exposed to ITU accumulated ADO in a time-dependent manner. Unstimulated chondrocytes did not accumulate ADO. Similarly, EHNA alone did not produce detectable ADO concentrations; however, addition of EHNA and ITU resulted in a synergistic effect on accumulation of ADO. Lipopolysaccharide-induced NO production was more effectively suppressed by exposure to ITU than to EHNA CONCLUSIONS AND CLINICAL RELEVANCE: Equine articular chondrocytes release ADO in response to the proinflammatory stimulus of bacterial LPS. Inhibition of the metabolism of ADO increases accumulation of extracellular ADO. Autocrine release of ADO from chondrocytes may play a role in the cellular response to tissue damage in arthritic conditions, and pharmacologic modulation of these pathways in joints of arthritic horses could be a potential method of therapy.
Publication Date: 2002-11-14 PubMed ID: 12428660DOI: 10.2460/ajvr.2002.63.1512Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Adenine Nucleotides
- Adenosine Triphosphate (ATP)
- Arthritis
- Articular Cartilage
- Biochemistry
- Cell Culture
- Chondrocytes
- Disease Treatment
- Enzymes
- Equine Health
- High-performance Liquid Chromatography (HPLC)
- Horses
- In Vitro Research
- Inflammation
- Lipopolysaccharide
- Metacarpophalangeal Joint
- Metatarsophalangeal Joint
- Nitric Oxide
- Pharmacology
- Veterinary Medicine
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research investigates how certain inhibitors affect the accumulation of a compound called adenosine by horse cartilage cells and also their production of nitric oxide – a molecule that plays a role in inflammation. Results suggest these pathways could be targeted to manage arthritic conditions in horses.
Research Methods
- Articular cartilage was harvested from the joints of 14 horses.
- The cells called chondrocytes from this cartilage were grown in culture.
- The researchers then exposed these cells to several substances: lipopolysaccharide (LPS) – a proinflammatory compound found in certain bacteria, an adenosine kinase inhibitor (5′-iodotubercidin, or ITU), and an adenosine deaminase inhibitor (EHNA).
- They measured the concentration of adenosine, a compound that plays various roles in cell signaling, in the cell supernatants using a method called reverse-phase high-performance liquid chromatography.
- The team studied the effect of these inhibitors on nitric oxide (NO) production, an important player in inflammation, by combining LPS with either ITU or EHNA and exposing the cells to these combinations.
Research Findings
- Chondrocytes exposed to either LPS or ITU accumulated extra adenosine outside their cells.
- When chondrocytes were treated with ITU, the cells accumulated adenosine in a time-dependent manner.
- No adenosine accumulation was observed in the chondrocytes if they were not stimulated, or if they were just exposed to EHNA.
- However, when the cells were treated with a combination of EHNA and ITU, an increased accumulation of adenosine was noted, suggesting a synergistic effect.
- The production of NO induced by LPS was more effectively reduced by ITU compared to EHNA.
Conclusions and Implications
- Equine articular chondrocytes released adenosine in response to an inflammatory stimulus – bacterial LPS.
- Inhibiting the metabolism of adenosine led to increased accumulation of this compound.
- The researchers propose an autocrine function for adenosine: its release from chondrocytes may play a role in the cell’s response to tissue damage in arthritis.
- This suggests potential therapeutic applications in modulating these pathways pharmacologically to treat arthritic conditions in horses.
Cite This Article
APA
Tesch AM, MacDonald MH, Kollias-Baker C, Benton HP.
(2002).
Effects of an adenosine kinase inhibitor and an adenosine deaminase inhibitor on accumulation of extracellular adenosine by equine articular chondrocytes.
Am J Vet Res, 63(11), 1512-1519.
https://doi.org/10.2460/ajvr.2002.63.1512 Publication
Researcher Affiliations
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
MeSH Terms
- Adenine / analogs & derivatives
- Adenine / pharmacology
- Adenosine / metabolism
- Adenosine Deaminase / metabolism
- Adenosine Deaminase Inhibitors
- Adenosine Kinase / antagonists & inhibitors
- Adenosine Kinase / metabolism
- Animals
- Cartilage, Articular / cytology
- Cartilage, Articular / drug effects
- Cartilage, Articular / enzymology
- Cartilage, Articular / metabolism
- Chondrocytes / drug effects
- Chondrocytes / enzymology
- Chondrocytes / metabolism
- Enzyme Inhibitors / pharmacology
- Horses / metabolism
- Lipopolysaccharides / metabolism
- Nitric Oxide / biosynthesis
- Nitrites / analysis
- Tubercidin / analogs & derivatives
- Tubercidin / pharmacology
Citations
This article has been cited 11 times.- Moretti L, Bizzoca D, Giancaspro GA, Cassano GD, Moretti F, Setti S, Moretti B. Biophysical Stimulation in Athletes' Joint Degeneration: A Narrative Review.. Medicina (Kaunas) 2021 Nov 4;57(11).
- Gratal P, Lamuedra A, Medina JP, Bermejo-Álvarez I, Largo R, Herrero-Beaumont G, Mediero A. Purinergic System Signaling in Metainflammation-Associated Osteoarthritis.. Front Med (Lausanne) 2020;7:506.
- Corciulo C, Castro CM, Coughlin T, Jacob S, Li Z, Fenyö D, Rifkin DB, Kennedy OD, Cronstein BN. Intraarticular injection of liposomal adenosine reduces cartilage damage in established murine and rat models of osteoarthritis.. Sci Rep 2020 Aug 10;10(1):13477.
- Corciulo C, Cronstein BN. Signaling of the Purinergic System in the Joint.. Front Pharmacol 2019;10:1591.
- Bekisz JM, Lopez CD, Corciulo C, Mediero A, Coelho PG, Witek L, Flores RL, Cronstein BN. The Role of Adenosine Receptor Activation in Attenuating Cartilaginous Inflammation.. Inflammation 2018 Aug;41(4):1135-1141.
- Haskó G, Antonioli L, Cronstein BN. Adenosine metabolism, immunity and joint health.. Biochem Pharmacol 2018 May;151:307-313.
- Li J, Dong S. The Signaling Pathways Involved in Chondrocyte Differentiation and Hypertrophic Differentiation.. Stem Cells Int 2016;2016:2470351.
- Strazzulla LC, Cronstein BN. Regulation of bone and cartilage by adenosine signaling.. Purinergic Signal 2016 Dec;12(4):583-593.
- Boison D. Adenosine kinase: exploitation for therapeutic gain.. Pharmacol Rev 2013 Jul;65(3):906-43.
- Mediero A, Cronstein BN. Adenosine and bone metabolism.. Trends Endocrinol Metab 2013 Jun;24(6):290-300.
- van Bergen CJ, Blankevoort L, de Haan RJ, Sierevelt IN, Meuffels DE, d'Hooghe PR, Krips R, van Damme G, van Dijk CN. Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial.. BMC Musculoskelet Disord 2009 Jul 10;10:83.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
