Defect-Related Luminescent Hydroxyapatite-Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells Via an ATP-Induced cAMP/PKA Pathway

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• 作者：Chao Wang ; Dandan Liu ; Cuimiao Zhang ; Jiadong Sun ; Weipei Feng ; Xing-Jie Liang ; Shuxiang Wang ; Jinchao Zhang
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：May 11, 2016
• 年：2016
• 卷：8
• 期：18
• 页码：11262-11271
• 全文大小：603K
• 年卷期：0
• ISSN：1944-8252

文摘

Novel defect-related hydroxyapatite (DHAP), which combines the advantages of HAP and defect-related luminescence, has the potential application in tissue engineering and biomedical area, because of its excellent capability of monitoring the osteogenic differentiation and material biodegradation. Although the extracellular mechanism of DHAP minerals and PO₄^3– functioning in osteogenic differentiation has been widely studied, the intracellular molecular mechanism through which PO₄^3– mediates osteogenesis of bone mesenchymal stem cells (BMSCs) is not clear. We examined a previously unknown molecular mechanism through which PO₄^3– promoted osteogenesis of BMSCs with an emphasis on adenosine–triphosphate (ATP)-induced cAMP/PKA pathway. Our studies showed that DHAP could be uptaken into lysosome, in which PO₄^3– was released from DHAP, because of the acid environment of lysosome. The released PO₄^3– interacted with ADP to form ATP, and then degraded into adenosine, an ATP metabolite, which interacted with A2b adenosine receptor to activate the cAMP/PKA pathway, resulting in the high expression of osteogenesis-related genes, such as Runx2, BMP-2, and OCN. These findings first revealed the function of ATP-metabolism in bone physiological homeostasis, which may be developed to cure bone metabolic diseases.