کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2130071 1086525 2015 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of P2×7 receptor in the differentiation of bone marrow stromal cells into osteoblasts and adipocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Role of P2×7 receptor in the differentiation of bone marrow stromal cells into osteoblasts and adipocytes
چکیده انگلیسی


• P2X7R activation increased osteogenesis and decrease adipogenesis in BMSCs.
• P2X7R activation ameliorated micro-architecture of trabecular bones in OVX mice.
• Number of adipocytes in bone marrow were decreased in BzATP-treated OVX mice.
• P2X7R regulated the differentiation of BMSCs by stimulating ERK1/2 and JNK.

Imbalance in osteogenesis and adipogenesis of bone marrow stromal cells is a crucial pathological process of osteoporosis. P2×7-deficient mice were previously shown to exhibit an osteopenic phenotype and abnormal fat distribution, leading us to hypothesize that P2×7R activation was involved in the differentiation of BMSCs. Consequently, we investigated the effect of P2×7R activation on osteogenic and adipogenic differentiation of BMSCs in vitro, and established an ovariectomized (OVX) osteoporosis model to test P2×7R activation on adipocytes formation, trabecular and cortical bone parameters in vivo. Our results showed that activation of P2×7R by BzATP resulted in increase in the gene expression of osteoblastic markers, the activity of alkaline phosphatase and bone mineralization, and decrease in the gene expression of adipogenic markers and the number of adipocytes generated by BMSCs. MicroCT analysis showed that BzATP treatment ameliorated the micro-architecture of trabecular bones in OVX mice, while cortical bone parameters were unaffected. H&E staining analysis showed that was increase in the volume of trabecular bone and number of trabecular bone, and decrease in bone marrow adipocytes in BzATP-treated OVX mice compared with OVX mice. Also, activation of P2×7R transduced to ERK1/2 and JNK signaling pathways. This transduction was prevented by BBG, U0126, and SP600125. U0126 and SP600125 prevented BzATP-induced up-regulation of osteogenic-related genes expression and down-regulation of adipogenic-related genes expression. These data suggest that BzATP activates the differentiation of BMSCs into osteoblasts but not adipocytes by stimulating ERK1/2 and JNK signaling pathways in a P2×7R-dependent way.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 339, Issue 2, 10 December 2015, Pages 367–379
نویسندگان
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