Adenosine receptor subtype expression and activation influence the differentiation of mesenchymal stem cells to osteoblasts and adipocytes
| Autor: | Borzo Gharibi, Jack Ham, Anju Ann Abraham, Bronwen Alice James Evans |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Blotting Western Peroxisome proliferator-activated receptor Cell Count Adenosine-5'-(N-ethylcarboxamide) Biology Calcification Physiologic Osteogenesis Internal medicine Adipocytes Cyclic AMP Purinergic P1 Receptor Agonists medicine Animals Humans Orthopedics and Sports Medicine Receptor QH426 chemistry.chemical_classification Adipogenesis Osteoblasts Mesenchymal stem cell Receptors Purinergic P1 Cell Differentiation Mesenchymal Stem Cells Osteoblast Alkaline Phosphatase Lipid Metabolism R1 Adenosine Adenosine receptor Rats Cell biology RUNX2 Endocrinology medicine.anatomical_structure Gene Expression Regulation Purinergic P1 Receptor Antagonists chemistry Biomarkers Signal Transduction medicine.drug |
| Zdroj: | Journal of Bone and Mineral Research. 26:2112-2124 |
| ISSN: | 0884-0431 |
| DOI: | 10.1002/jbmr.424 |
| Popis: | Osteoblasts and adipocytes differentiate from a common precursor cell, the mesenchymal stem cell (MSC). Adenosine is known to signal via four adenosine receptor subtypes, and significantly, recent findings indicate that these may play a role in MSC differentiation. We therefore investigated adenosine receptor expression and activation during the differentiation of MSCs to osteoblasts and adipocytes. The A(2B) R was dominant in MSCs, and its expression and activity were transiently upregulated at early stages of osteoblastic differentiation. Both activation and overexpression of A(2B) R induced the expression of osteoblast-related genes [Runx2 and alkaline phosphatase (ALP)], as well as ALP activity, and stimulation increased osteoblast mineralization. The expression of A(2A) R was upregulated during later stages of osteoblastic differentiation, when its activation stimulated ALP activity. Differentiation of MSCs to adipocytes was accompanied by significant increases in A(1) R and A(2A) R expression, and their activation was associated with increased adipogenesis. Enhanced A(2A) R expression was sufficient to promote expression of adipocyte-related genes (PPARγ and C/EBPα), and its activation resulted in increased adipocytic differentiation and lipid accumulation. In contrast, the A(1) R was involved mainly in lipogenic activity of adipocytes rather than in their differentiation. These results show that adenosine receptors are differentially expressed and involved in lineage-specific differentiation of MSCs. We conclude, therefore, that fruitful strategies for treating diseases associated with an imbalance in the differentiation and function of these lineages should include targeting adenosine receptor signal pathways. Specifically, these research avenues will be useful in preventing or treating conditions with insufficient bone or excessive adipocyte formation. |
| Databáze: | OpenAIRE |
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