Regulation of bone and cartilage by adenosine signaling

Strazzulla, Lauren C.; Cronstein, Bruce N.

doi:10.1007/s11302-016-9527-2

Cited by 44 publications

(41 citation statements)

References 99 publications

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“…Owing to its effects on osteoclasts and macrophages and production of proinflammatory cytokines, A 2a also inhibits inflammatory bone damage induced by prosthetic wear particles 97 . Interestingly, both A 2a and A 2b stimulate bone formation in vivo 98 although only the direct stimulatory effects of A 2b on osteoblast function have been well characterized 99,100 .…”

Section: Adenosine Receptors and Innate Immunitymentioning

confidence: 99%

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Cronstein¹,

2016

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Adenosine, a nucleoside derived primarily from the extracellular hydrolysis of adenine nucleotides, is a potent regulator of inflammation. Adenosine mediates its effects on inflammatory cells by engaging one or more cell-surface receptors. The expression and function of adenosine receptors on different cell types change during the course of rheumatic diseases, such as rheumatoid arthritis. Targeting adenosine receptors directly for the treatment of rheumatic diseases is currently under study; however, indirect targeting of adenosine receptors by enhancing adenosine levels at inflamed sites accounts for most of the anti-inflammatory effects of methotrexate, the anchor drug for the treatment of rheumatoid arthritis. In this Review, we discuss the regulation of extracellular adenosine levels and the role of adenosine in regulating the inflammatory and immune responses in rheumatic diseases such as Rheumatoid Arthritis, psoriasis and other types of inflammatory arthritis. In addition, adenosine and its receptors are involved in promoting fibrous matrix production in the skin and other organs and the role of adenosine in fibrosis and fibrosing diseases will also be discussed.

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Section: Adenosine Receptors and Innate Immunitymentioning

confidence: 99%

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Cronstein¹,

2016

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“…As also shown in this study, activation of A 3 AR by its agonists such as adenosine, CADO, and IB-MECA inhibited TNAP expression and in vitro calcification in HASMCs, suggesting that adenosine may inhibit osteoblastic differentiation of VSMCs through A 3 AR. It has been clarified that ARs play a pivotal role in osteoblast differentiation and function (Strazzulla and Cronstein 2016).…”

Section: Discussionmentioning

confidence: 99%

Adenosine Attenuates Aortic Smooth Muscle Cell Calcification through A<sub>3</sub> Adenosine Receptor

Fujimoto

Shioi

Miki

et al. 2019

Tohoku J. Exp. Med.

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Vascular calcification is a typical feature of atherosclerosis and is associated with adverse cardiovascular events such as myocardial infarction and stroke. Several studies have suggested that adenosine, an ATP metabolite may function as an endogenous regulator of arterial calcification. However, its effects on vascular smooth muscle cell calcification have not been clarified. In this study, we investigated the inhibitory effects of adenosine on vascular calcification in vitro by utilizing the culture of human aortic smooth muscle cells (HASMCs). Osteoblastic differentiation of HASMCs was induced by the treatment with oncostatin M and osteogenic differentiation medium. Adenosine and its metabolically stable analogue, 2-chloroadenosine (CADO) significantly reduced matrix mineralization and alkaline phosphatase (ALP) activities in HASMCs. The mRNA expression of tissue non-specific alkaline phosphatase (TNAP) was down-regulated by adenosine and CADO, but the mRNA expression of other osteoblastic differentiation markers, such as Runt-related transcription factor 2 (RUNX2) and bone sialoprotein (BSP)-II, was not significantly affected by these two reagents. Among the adenosine receptor (AR) subtype-selective agonists used, only IB-MECA (A 3 AR-selective agonist) significantly decreased in vitro mineralization and ALP activities in HASMCs, but not with CCPA (A 1 AR-selective agonist), CGS21680 (A 2a AR-selective agonist), or BAY60-6583 (A 2b AR-selective agonist). Importantly, IB-MECA also down-regulated expression of TNAP mRNA. Finally, knockdown of A 3 AR, but not A 1 AR, A 2a AR, or A 2b AR, significantly reversed the inhibitory actions of adenosine, CADO, or IB-MECA on in vitro calcification and ALP activities in HASMCs. These data suggest that adenosine attenuates HASMC calcification through A 3 AR.

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“…The result of increased purine metabolism may correspond to known adenosine signaling regulating bone and cartilage health (Strazzulla and Cronstein, 2016). The intracellular and extracellular production of adenosine, a purine nucleoside, acts in response to mechanical stimulation including inflammation.…”

Section: Discussionmentioning

confidence: 99%

Metabolic responses induced by compression of chondrocytes in variable-stiffness microenvironments

McCutchen

Zignego

June

2017

Journal of Biomechanics

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Cells sense and respond to mechanical loads in a process called mechanotransduction. These processes are disrupted in the chondrocytes of cartilage during joint disease. A key driver of cellular mechanotransduction is the stiffness of the surrounding matrix. Many cells are surrounded by extracellular matrix that allows for tissue mechanical function. Although prior studies demonstrate that extracellular stiffness is important in cell differentiation, morphology and phenotype, it remains largely unknown how a cell’s biological response to cyclical loading varies with changes in surrounding substrate stiffness. Understanding these processes is important for understanding cells that are cyclically loaded during daily in vivo activities (e.g. chondrocytes and walking). This study uses high-performance liquid chromatography - mass spectrometry to identify metabolomic changes in primary chondrocytes under cyclical compression for 0–30 minutes in low- and high- stiffness environments. Metabolomic analysis reveals metabolites and pathways that are sensitive to substrate stiffness, duration of cyclical compression, and a combination of both suggesting changes in extracellular stiffness in vivo alter mechanosensitive signaling. Our results further suggest that cyclical loading minimizes matrix deterioration and increases matrix production in chondrocytes. This study shows the importance of modeling in vivo stiffness with in vitro models to understand cellular mechanotransduction.

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Regulation of bone and cartilage by adenosine signaling

Cited by 44 publications

References 99 publications

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Adenosine Attenuates Aortic Smooth Muscle Cell Calcification through A<sub>3</sub> Adenosine Receptor

Metabolic responses induced by compression of chondrocytes in variable-stiffness microenvironments

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