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Human Osteoblast Precursors Produce Extracellular Adenosine, Which Modulates Their Secretion of IL-6 and Osteoprotegerin
- Source :
- Journal of Bone and Mineral Research. 21:228-236
- Publication Year :
- 2005
- Publisher :
- Wiley, 2005.
-
Abstract
- We showed that human osteoprogenitor cells produced adenosine and expressed ecto-5?-nucleotidase and all four adenosine receptor subtypes. Adenosine stimulated IL-6 but inhibited osteoprotegerin secretion, suggesting that adenosine is a newly described regulator of progenitor cell function. Introduction: Maintaining skeletal homeostasis relies on there being a balance between bone formation and resorption; an imbalance between these processes can lead to diseases such as osteoporosis and rheumatoid arthritis. Recent reports showed that locally produced ATP, acting through P2 receptors, has pronounced effects on bone formation. However, ATP can be enzymatically cleaved to adenosine that has little or no activity at P2 receptors but mediates its action through the P1 family of receptors. We studied whether adenosine may also have an important role in controlling bone cell differentiation and function. Materials and Methods: Extracellular adenosine levels were analyzed by high-performance liquid chromatography in HCC1 and bone marrow stromal (BMS) cells. Ecto-5?-nucleotidase (CD73) expression and activity was determined by RT-PCR, immunocytochemistry, and the cleavage of etheno-AMP to ethenoadenosine. Adenosine receptor expression and activity were determined by RT-PCR and cAMP measurements. The effects of adenosine receptor agonists on IL-6, osteoprotegerin (OPG), and RANKL expression were determined by ELISA and QRT-PCR. Results: HCC1 and BMS cells produce adenosine and express CD73 and all four adenosine receptor subtypes. The A2b receptor was shown to be functionally dominant in HCC1 cells, as determined by cAMP production and in its stimulation of IL-6 secretion. Adenosine receptor agonism also inhibited OPG secretion and OPG but not RANKL mRNA expression. Conclusions: Our findings show that HCC1 and primary BMS cells produce adenosine, express CD73 and all four adenosine receptor subtypes. In HCC1 cells, adenosine has a potent stimulatory action on IL-6 secretion but an inhibitory action on OPG expression. These data show for the first time that adenosine may be an important regulator of progenitor cell differentiation and hence an important local contributor to the regulation of bone formation and resorption.
- Subjects :
- medicine.medical_specialty
Adenosine
Adenosine Deaminase
Endocrinology, Diabetes and Metabolism
Receptors, Cytoplasmic and Nuclear
Bone Marrow Cells
Receptors, Tumor Necrosis Factor
Adenosine A1 receptor
Osteoprotegerin
Internal medicine
Purinergic P1 Receptor Agonists
medicine
Humans
Orthopedics and Sports Medicine
5'-Nucleotidase
Adenosine Kinase
Glycoproteins
Membrane Glycoproteins
Osteoblasts
Receptor Activator of Nuclear Factor-kappa B
biology
Interleukin-6
Stem Cells
RANK Ligand
Receptors, Purinergic P1
Cell Differentiation
Purinergic signalling
Adenosine A3 receptor
Adenosine receptor
Protein Transport
Endocrinology
RANKL
biology.protein
Stromal Cells
Carrier Proteins
Adenosine A2B receptor
medicine.drug
Subjects
Details
- ISSN :
- 08840431
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Journal of Bone and Mineral Research
- Accession number :
- edsair.doi.dedup.....46b471ffab33323fb667d47959228eba