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Vascular Calcifying Progenitor Cells Possess Bidirectional Differentiation Potentials
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نویسنده
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cho h.-j. ,cho h.-j. ,lee h.-j. ,song m.-k. ,seo j.-y. ,bae y.-h. ,kim j.-y. ,lee h.-y. ,lee w. ,koo b.-k. ,oh b.-h. ,park y.-b. ,kim h.-s.
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منبع
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plos biology - 2013 - دوره : 11 - شماره : 4
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چکیده
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Vascular calcification is an advanced feature of atherosclerosis for which no effective therapy is available. to investigate the modulation or reversal of calcification,we identified calcifying progenitor cells and investigated their calcifying/decalcifying potentials. cells from the aortas of mice were sorted into four groups using sca-1 and pdgfrα markers. sca-1+ (sca-1+/pdgfrα+ and sca-1+/pdgfrα-) progenitor cells exhibited greater osteoblastic differentiation potentials than sca-1- (sca-1-/pdgfrα+ and sca-1-/pdgfrα-) progenitor cells. among sca-1+ progenitor populations,sca-1+/pdgfrα- cells possessed bidirectional differentiation potentials towards both osteoblastic and osteoclastic lineages,whereas sca-1+/pdgfrα+ cells differentiated into an osteoblastic lineage unidirectionally. when treated with a peroxisome proliferator activated receptor γ (pparγ) agonist,sca-1+/pdgfrα- cells preferentially differentiated into osteoclast-like cells. sca-1+ progenitor cells in the artery originated from the bone marrow (bm) and could be clonally expanded. vessel-resident bm-derived sca-1+ calcifying progenitor cells displayed nonhematopoietic,mesenchymal characteristics. to evaluate the modulation of in vivo calcification,we established models of ectopic and atherosclerotic calcification. computed tomography indicated that sca-1+ progenitor cells increased the volume and calcium scores of ectopic calcification. however,sca-1+/pdgfrα- cells treated with a pparγ agonist decreased bone formation 2-fold compared with untreated cells. systemic infusion of sca-1+/pdgfrα- cells into apoe-/- mice increased the severity of calcified atherosclerotic plaques. however,sca-1+/pdgfrα- cells in which pparγ was activated displayed markedly decreased plaque severity. immunofluorescent staining indicated that sca-1+/pdgfrα- cells mainly expressed osteocalcin; however,activation of pparγ triggered receptor activator for nuclear factor-κb (rank) expression,indicating their bidirectional fate in vivo. these findings suggest that a subtype of bm-derived and vessel-resident progenitor cells offer a therapeutic target for the prevention of vascular calcification and that pparγ activation may be an option to reverse calcification. © 2013 cho et al.
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آدرس
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national research laboratory for stem cell niche,seoul national university college of medicine,seoul,south korea,cardiovascular center and department of internal medicine,seoul national university hospital,seoul,south korea,innovative research institute for cell therapy,seoul national university hospital,seoul, South Korea, national research laboratory for stem cell niche,seoul national university college of medicine,seoul,south korea,cardiovascular center and department of internal medicine,seoul national university hospital,seoul,south korea,innovative research institute for cell therapy,seoul national university hospital,seoul, South Korea, national research laboratory for stem cell niche,seoul national university college of medicine,seoul,south korea,innovative research institute for cell therapy,seoul national university hospital,seoul, South Korea, national research laboratory for stem cell niche,seoul national university college of medicine,seoul,south korea,innovative research institute for cell therapy,seoul national university hospital,seoul, South Korea, national research laboratory for stem cell niche,seoul national university college of medicine,seoul, South Korea, national research laboratory for stem cell niche,seoul national university college of medicine,seoul,south korea,innovative research institute for cell therapy,seoul national university hospital,seoul, South Korea, national research laboratory for stem cell niche,seoul national university college of medicine,seoul,south korea,innovative research institute for cell therapy,seoul national university hospital,seoul, South Korea, cardiovascular center and department of internal medicine,seoul national university hospital,seoul, South Korea, department of radiology,seoul national university college of medicine,seoul, South Korea, cardiovascular center and department of internal medicine,seoul national university hospital,seoul, South Korea, cardiovascular center and department of internal medicine,seoul national university hospital,seoul, South Korea, cardiovascular center and department of internal medicine,seoul national university hospital,seoul,south korea,innovative research institute for cell therapy,seoul national university hospital,seoul, South Korea, national research laboratory for stem cell niche,seoul national university college of medicine,seoul,south korea,cardiovascular center and department of internal medicine,seoul national university hospital,seoul,south korea,innovative research institute for cell therapy,seoul national university hospital,seoul,south korea,world class university program,department of molecular medicine and biopharmaceutical sciences,seoul national university,seoul, South Korea
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Authors
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