Adenosinergic signalling in chondrogenesis and cartilage homeostasis: Friend or foe?

• Type: Another Publication in an International Scientific Journal
• Date: 2020

Authors

Pinto Cardoso, R (Author) Other; Pereira Costa, F (Author) Other; Pedro Faria, J (Author) Other; Bandarrinha, P (Author) Other; Bessa Andrês, C (Author) Other; Correia de Sá, P (Author) Other; Bernardo Noronha Matos, J (Author) ICBAS

Journal

Title: Biochemical Pharmacology

Vol. 174

ISSN: 0006-2952

Publisher: Elsevier

Indexing

Scopus - 0 Citations

Other information

Authenticus ID: P-00R-HFK

DOI: 10.1016/j.bcp.2019.113784

Abstract (EN): 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, PGE2 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-1¿ overexpression, resulting in disproportionate ecto-5¿-nucleotidase/CD73 production, adenosine accumulation and superfluous A2B receptors activation. Scarcity of data however exists on the putative interplay between coexistent high affinity (A2A and A3) and low affinity (A2B) 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 A2A and A3 receptors having cartilage protective roles, while excessive adenosine accumulation may be detrimental via low affinity A2B 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. © 2019 Elsevier Inc.

Language: English

Type (Professor's evaluation): Scientific