Naslov
Evaluation of αSMA Expressing Cell Contribution To Muscle Heterotopic Ossification

Autori
Torreggiani, Elena ; Grčević, Danka ; Matthews, Brya ; Kalajzić, Ivo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Journal of bone and mineral research / ASBMR - , 2012

Skup
ASBMR Annual Meeting 2012

Mjesto i datum
Minneapolis (MN), Sjedinjene Američke Države, 14.10.2012. - 18.10.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
muscle progenitor cells; heterotopic ossification

Sažetak
Heterotopic ossification is characterized by the formation of bone in atypical locations including muscle and subcutaneous tissues. Enormous progress has been made in understanding the identity of the cells that participate in the lesion formation, and molecular mechanisms underlaying the induction of the osteogenic commitment. Several studies addressed to identify the role of BMP signaling in the heterotopic ossification have been performed. However, the identity of progenitor cells that contribute to BMP-induced heterotopic ossification is still unknown. The aim of our current work is to evaluate whether the cells that reside in the perivascular niche can actively contribute to the bone formation. We have observed the expression of a smooth muscle a-actin promoter directed green fluorescent promoter (αSMA-GFP) in the perivascular location in both muscle and subcutaneous tissue. The critical evidence of the transition of the cellular phenotype can be obtained by combinatorial approach of using visual markers for transgene expression and Cre/loxP recombination system that will allow for the lineage tracing. Therefore we have bred αSMACreERT2 mice with reporter mice in which RFP Tomato expression is controlled by ubiquitious promoter and dependent on Cre activation by tamoxifen. To assess the transition of αSMA expressing cells to osteoblast lineage we have used a bone specific Col2.3 promoter driving GFP. These mice were intercrossed to generate a triple transgenic model αSMACreERT2/Ai9/Col2.3GFP. Heterotopic ossification was induced by intramuscular injection of 2.5µg of BMP2/Matrigel. The formation of bone ossicles was evaluated by x-ray analysis and mice were sacrificed at different time points. The contribution of αSMACreERT2/Ai9 labeled cells to bone was evaluated using fluorescence microscopy. Our results suggest that aSMA expressing cells can give rise to a population of mature osteoblasts present within heterotopic lesions. Currently, we directed our efforts to better define the cellular phenotype of the αSMACreERT2/Ai9 labeled progenitor cells. We plan to evaluate the αSMACreERT2/Ai9 expression to the presence of endothelial (CD31), hematopoietic (CD45), satellite cells (SM/C2.6) and mesenchymal stem cells (PDGFRα, PDGFRβ and Sca1) markers by flow cytometry. This study provides new insight into the cellular identity of cells that participate in the formation of the heterotopic ossification.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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