Differentiation of mesenchymal stem cells to osteoblasts and chondrocytes: a focus on adenosine receptors

Osteoarthritis (OA) is the most common form of chronic musculoskeletal disorders. A migratory stem cell population termed chondrogenic progenitor cells (CPC) with in vitro chondrogenic potential was previously isolated from OA cartilage. Since intracellular Ca 2+ signalling is an important regulator of chondrogenesis, we aimed to provide a detailed understanding of the Ca 2+ homeostasis of CPCs. In this work, CPCs immortalised by lentiviral administration of the human telomerase reverse transcriptase (hTERT) and grown in monolayer cultures were studied. Expressions of all three IP3Rs were confirmed, but no RyR subtypes were detected. Ca 2+ oscillations observed in CPCs were predominantly dependent on Ca 2+ release and store replenishment via store-operated Ca 2+ entry; CPCs express both STIM1 and Orai1 proteins. Expressions of adenosine receptor mRNAs were verified, and adenosine elicited Ca 2+ transients. Various P2 receptor subtypes were identified; P2Y1 can bind ADP; P2Y4 is targeted by UTP; and ATP may evoke Ca 2+ transients via detected P2X subtypes, as well as P2Y1 and P2Y2. Enzymatic breakdown of extracellular nucleotides by apyrase completely abrogated Ca 2+ oscillations, suggesting that an autocrine/paracrine purinergic mechanism may drive Ca 2+ oscillations in these cells.As CPCs possess a broad spectrum of functional molecular elements of Ca 2+ signalling, Ca 2+ -dependent regulatory mechanisms can be supposed to influence their differentiation potential.

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“…For further details, the authors refer the reader to a recently published review article in this field [5].…”

Section: Purinergic Signalling In Cpcs and Autocrine/paracrine Regulamentioning

confidence: 99%

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

Matta

Fodor

Miosge

et al. 2014

Pflugers Arch - Eur J Physiol

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“…It should be noted that the same P1 receptor subtypes were found to be expressed in articular chondrocytes [87]. A 2A and A 2B adenosine receptors are of particular importance as these are coupled to G s , which stimulates AC and produces a cAMP signal [88]; cAMP mediated signalling is a well known mediator of chondrogenesis as well as in maintaining the chondrocyte phenotype [89].…”

Section: P1 Adenosine Receptor Expression and Function During Chondromentioning

confidence: 97%

Purinergic signalling-evoked intracellular Ca2+ concentration changes in the regulation of chondrogenesis and skeletal muscle formation

et al. 2016

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“…Repair of the skeletal system depends on the differentiation of osteoblasts from their progenitors (mesenchymal stem cells, MSCs) which have a broad, multilineage differentiation potential and express A1, A2A, A2B, and A3 receptors [67,68] (see Fig. 3).…”

Section: Regulation Of Osteoblast Differentiation and Function By Adementioning

confidence: 99%

“…Adenosine promotes osteoblast differentiation primarily through the A2BR receptor [68,78,80]. Rao et al showed that A2B receptors may be integral in the maturation of bone tissue, as their expression increases as a function of time [81].…”

Section: P1 Receptors: A2brmentioning

confidence: 99%

“…Rao et al showed that A2B receptors may be integral in the maturation of bone tissue, as their expression increases as a function of time [81]. A2BR knockout mice have MSCs with decreased osteogenic potential in addition to lower bone density and delayed fracture repair [68]. Trincalvelli et al used an allosteric modulator of A2BR, KI-7, and found this molecule-enhanced MSC differentiation to osteoblasts by increasing expression of osteoblast genes and accelerating osteoblast mineralization [82].…”

Section: P1 Receptors: A2brmentioning

confidence: 99%

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Regulation of bone and cartilage by adenosine signaling

Strazzulla

Cronstein

2016

Purinergic Signalling

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There is growing recognition that bone serves important endocrine and immunologic functions that are compromised in several disease states. While many factors are known to affect bone metabolism, recent attention has focused on investigating the role of purinergic signaling in bone formation and regulation. Adenosine is a purine nucleoside produced intracellularly and extracellularly in response to stimuli such as hypoxia and inflammation, which then interacts with P1 receptors. Numerous studies have suggested that these receptors play a pivotal role in osteoblast, osteoclast, and chondrocyte differentiation and function. This review discusses the various ways by which adenosine signaling contributes to bone and cartilage homeostasis, while incorporating potential therapeutic applications of these signaling pathways.

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Differentiation of mesenchymal stem cells to osteoblasts and chondrocytes: a focus on adenosine receptors

Cited by 47 publications

References 125 publications

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

Purinergic signalling is required for calcium oscillations in migratory chondrogenic progenitor cells

Purinergic signalling-evoked intracellular Ca2+ concentration changes in the regulation of chondrogenesis and skeletal muscle formation

Regulation of bone and cartilage by adenosine signaling

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