10.3389/fimmu.2019.01640.s002
Mario Tirone
Mario
Tirone
Anna Giovenzana
Anna
Giovenzana
Arianna Vallone
Arianna
Vallone
Paola Zordan
Paola
Zordan
Martina Sormani
Martina
Sormani
Pier Andrea Nicolosi
Pier Andrea
Nicolosi
Raffaela Meneveri
Raffaela
Meneveri
Carmen Rosaria Gigliotti
Carmen Rosaria
Gigliotti
Antonello E. Spinelli
Antonello E.
Spinelli
Renata Bocciardi
Renata
Bocciardi
Roberto Ravazzolo
Roberto
Ravazzolo
Ingrid Cifola
Ingrid
Cifola
Silvia Brunelli
Silvia
Brunelli
Image_2_Severe Heterotopic Ossification in the Skeletal Muscle and Endothelial Cells Recruitment to Chondrogenesis Are Enhanced by Monocyte/Macrophage Depletion.tif
Frontiers
2019
macrophage
endothelial cell (EC)
heterotopic ossification (HO)
EndoMT
endothelial progenitors cells
RNASeq and NGS data analysis
micro-computerized tomography (μCT) analysis
2019-07-22 14:19:12
Figure
https://frontiersin.figshare.com/articles/figure/Image_2_Severe_Heterotopic_Ossification_in_the_Skeletal_Muscle_and_Endothelial_Cells_Recruitment_to_Chondrogenesis_Are_Enhanced_by_Monocyte_Macrophage_Depletion_tif/8977133
<p>Altered macrophage infiltration upon tissue damage results in inadequate healing due to inappropriate remodeling and stem cell recruitment and differentiation. We investigated in vivo whether cells of endothelial origin phenotypically change upon heterotopic ossification induction and whether infiltration of innate immunity cells influences their commitment and alters the ectopic bone formation. Liposome-encapsulated clodronate was used to assess macrophage impact on endothelial cells in the skeletal muscle upon acute damage in the ECs specific lineage-tracing Cdh5CreER<sup>T2</sup>:R26REYFP/dtTomato transgenic mice. Macrophage depletion in the injured skeletal muscle partially shifts the fate of ECs toward endochondral differentiation. Upon ectopic stimulation of BMP signaling, monocyte depletion leads to an enhanced contribution of ECs chondrogenesis and to ectopic bone formation, with increased bone volume and density, that is reversed by ACVR1/SMAD pathway inhibitor dipyridamole. This suggests that macrophages contribute to preserve endothelial fate and to limit the bone lesion in a BMP/injury-induced mouse model of heterotopic ossification. Therefore, alterations of the macrophage-endothelial axis may represent a novel target for molecular intervention in heterotopic ossification.</p>