Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Adenosine A2A Antagonist ZM241385 Increases Osteoblast Differentiation and Function In Vitro.
Ziglar2, Louisa, Cronstein1, Bruce N.
Adenosine, a potent endogenous physiological mediator, regulates a wide variety of physiological processes via interaction with one or more of four G protein-coupled receptors (A1, A2a, A2b, and A3), expressed on many cell types. Because we have reported that adenosine receptors affect bone mineral density (BMD), we determined whether adenosine, acting through one or another of these receptors, regulated the formation of osteoblasts and their function in vitro.
Murine MC3T3-E1 Osteoblast precursor cells were cultured for 12 or 21 days in alpha-MEM media with vitamin C and beta-glycerolphosphate enrichment. Adenosine receptor A1 and A2a agonist and antagonist were added individually at a concentration of 10-6 mg/ml. To evaluate osteoblast differentiation, alkaline phosphatase (ALP) assay activity was performed on day 12. Alizarin red activity was measured on day 21 to evaluate osteoblast function. Experiment was performed in triplicate.
Our preliminary results report no significant difference in osteoblast differentiation using A1 receptor treatment and increased differentiation and function under the presence of adenosine A2A antagonist ZM241385. Alizarin red activity showed no significant difference from control in the presence of A1 receptor agonist or antagonist where the A2A antagonist showed increased activity by 71% (p<0.001 n=1). Cells treated with ZM241385 showed an increase in ALP activity by 53% (p=0.19 n=1).
Adenosine receptors are targets for a variety of drugs, including anti-inflammatory drugs (e.g. adenosine mediates the anti-inflammatory effects of low-dose methotrexate in the treatment of Rheumatoid Arthritis). Other indications are currently under study in pre-clinical and clinical studies. Our results suggest that adenosine A2A receptors may be potential targets for the treatment of bone disease as well.
To cite this abstract, please use the following information:
Ziglar, Louisa, Cronstein, Bruce N.; Adenosine A2A Antagonist ZM241385 Increases Osteoblast Differentiation and Function In Vitro. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :956