Adenosinergic signalling in chondrogenesis and cartilage homeostasis: Friend or foe?
Abstract: Chondrocytes and their mesenchymal cell progenitors secrete a variety of bioactive molecules, including adenine nucleotides and nucleosides, but these molecules are not usually highlighted in review papers about the secretome of these cells. Ageing and inflammatory insults compromise chondrocytes ability to keep ATP/adenosine synthesis, release and turnover. Cartilage homeostasis depends on extracellular adenosine levels, which acting via four P1 purinoceptor subtypes modulates the release of pro-inflammatory mediators, including NO, PGE and several cytokines. Native articular cartilage is challenged by synovial fluid flow during normal joint motion transiently increasing ATP release and adenosine formation in the joint microenvironment. Excessive joint motion and shockwave trauma are deleterious to cartilage homeostasis due to HIF-1α overexpression, resulting in disproportionate ecto-5'-nucleotidase/CD73 production, adenosine accumulation and superfluous A receptors activation. Scarcity of data however exists on the putative interplay between coexistent high affinity (A and A) and low affinity (A) adenosine receptors activation affecting stem cells fate towards preferential chondrogenic or osteogenic lineages in the human cartilage. Hints gathered in this commentary result mainly from studies using human immortalized cell lines and animal (e.g. rodent, equine, bovine) tissue samples. The available data point towards adenosine A and A receptors having cartilage protective roles, while excessive adenosine accumulation may be detrimental via low affinity A receptors activation, with little reference to the putative role of the adenosine forming enzyme ecto-5'-nucleotidase/CD73. Thus, emphasizing the multiple pathways responsible for controlling adenosine signalling in cartilage will certainly impact on the search for novel therapeutic targets for highly disabling articular disorders.
Copyright © 2019 Elsevier Inc. All rights reserved.
Publication Date: 2019-12-26 PubMed ID: 31884043DOI: 10.1016/j.bcp.2019.113784Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Review
Summary
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This research investigates the role of adenosinergic signalling in the maintenance and formation of cartilage tissue. Findings suggest that while some aspects of adenosinergic signalling can be beneficial for cartilage health, excessive adenosine accumulation may cause harm.
Overview of the Research
- The paper discusses the process of chondrogenesis, which is essentially the formation and development of cartilage in the body. This process is spearheaded by cells known as chondrocytes and their forerunners, termed as mesenchymal cells.
- Despite these cells secreting a variety of molecules including adenine nucleotides and nucleosides, such molecules are often overlooked, which this research aims to illuminate.
- The researchers specifically delve into the potential implications of ATP/adenosine synthesis, release, and turnover in regards to cartilage health or homeostasis. The implications of this research extend to understanding the role of extracellular adenosine levels in mitigating inflammatory reactions.
Adenosine and Cartilage Homeostasis
- In the context of cartilage homeostasis, the balance of adenosine presence in the extracellular environment is critical. Normal joint motion causes incremental increases in ATP release and subsequent adenosine formation.
- However, when exposed to excessive motion or shockwave trauma, an overabundance of HIF-1α can be harmful. This overexpression is linked to disproportionate production of ecto-5′-nucleotidase/CD73, leading to adenosine accumulation and a potential overactivation of adenosine receptors, which can disrupt cartilage homeostasis.
Role of Adenosine Receptors
- The study also hints at a potential interplay between the activation of various adenosine receptors and the fate of stem cells, noting that higher affinity receptors may promote cartilage formation, while lower affinity receptors could potentially contribute to osteogenic (bone-producing) lineage preference.
- Findings from the study suggest adenosine A and A receptors may provide cartilage-protective roles, while excessive adenosine accumulation may harm low-affinity A receptors.
- The role of ecto-5′-nucleotidase/CD73, an enzyme responsible for the formation of adenosine, is somewhat understated.
Implications and Future Research
- With a greater understanding of the multiple pathways controlling adenosine signalling in cartilage, the research concludes that such knowledge can inform strategies for novel therapies targeting articular disorders, which are currently highly disabling.
- This can be viewed as a urging call for more in-depth studies on the multiple roles adenosinergic signalling plays in cartilage homeostasis – an area overlooked in academic discourse thus far – in order to enhance therapeutic efficacy against numerous disabling disorders.
Cite This Article
APA
Pinto-Cardoso R, Pereira-Costa F, Pedro Faria J, Bandarrinha P, Bessa-Andrês C, Correia-de-Sá P, Bernardo Noronha-Matos J.
(2019).
Adenosinergic signalling in chondrogenesis and cartilage homeostasis: Friend or foe?
Biochem Pharmacol, 174, 113784.
https://doi.org/10.1016/j.bcp.2019.113784 Publication
Researcher Affiliations
- Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal.
- Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal.
- Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal.
- Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal.
- Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal.
- Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal. Electronic address: farmacol@icbas.up.pt.
- Laboratório de Farmacologia e Neurobiologia, Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal; Center for Drug Discovery and Innovative Medicines (MedInUP), Departamento de Imuno-Fisiologia e Farmacologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal. Electronic address: jbmatos@icbas.up.pt.
MeSH Terms
- Adenosine / metabolism
- Aging / metabolism
- Animals
- Cartilage, Articular / metabolism
- Chondrocytes / immunology
- Chondrocytes / metabolism
- Chondrogenesis / immunology
- Chondrogenesis / physiology
- Homeostasis
- Humans
- Inflammation
- Receptors, Purinergic P1 / metabolism
- Signal Transduction
Citations
This article has been cited 4 times.- Noronha-Matos JB, Pinto-Cardoso R, Bessa-Andrês C, Magalhães-Cardoso MT, Ferreirinha F, Costa MA, Marinhas J, Freitas R, Lemos R, Vilaça A, Oliveira A, Pelletier J, Sévigny J, Correia-de-Sá P. Silencing NTPDase3 activity rehabilitates the osteogenic commitment of post-menopausal stem cell bone progenitors.. Stem Cell Res Ther 2023 Apr 19;14(1):97.
- Giuliani AL, Sarti AC, Di Virgilio F. Ectonucleotidases in Acute and Chronic Inflammation.. Front Pharmacol 2020;11:619458.
- Varani K, Vincenzi F, Pasquini S, Blo I, Salati S, Cadossi M, De Mattei M. Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications.. Int J Mol Sci 2021 Jan 15;22(2).
- 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.
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