Monocyte Exosomes Stimulate the Osteogenic Gene Expression of Mesenchymal Stem CellsReportar como inadecuado




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Inflammation and regeneration at the implant-bone interface are intimately coupled via cell-cell communication. In contrast to the prevailing view that monocytes-macrophages orchestrate mesenchymal stem cells MSCs and progenitor cells via the secretion of soluble factors, we examined whether communication between these different cell types also occurs via exosomes. LPS-stimulated human monocytes released exosomes, positive for CD9, CD63, CD81, Tsg101 and Hsp70, as determined by flow cytometry and Western blot. These exosomes also contained wide size distribution of RNA, including RNA in the size of microRNAs. The exosomes were shown to interact with human mesenchymal stem cells. After 24 h of culture, a considerable portion of the MSCs had internalised PKH67-labelled exosomes. Furthermore, after 72 h, the gene expression of the osteogenic markers runt-related transcription factor 2 RUNX2 and bone morphogenetic protein-2 BMP-2 had increased in comparison with control medium, whereas no significant difference in osteocalcin OC expression was demonstrated. The present results show that, under given experimental conditions, monocytes communicate with MSCs via exosomes, resulting in the uptake of exosomes in MSCs and the stimulation of osteogenic differentiation. The present observations suggest that exosomes constitute an additional mode of cell-cell signalling with an effect on MSC differentiation during the transition from injury and inflammation to bone regeneration.



Autor: Karin Ekström , Omar Omar, Cecilia Granéli, Xiaoqin Wang, Forugh Vazirisani, Peter Thomsen

Fuente: http://plos.srce.hr/



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