دورية أكاديمية

Vascular calcifying progenitor cells possess bidirectional differentiation potentials.

التفاصيل البيبلوغرافية
العنوان: Vascular calcifying progenitor cells possess bidirectional differentiation potentials.
المؤلفون: Hyun-Ju Cho, Hyun-Jai Cho, Ho-Jae Lee, Myung-Kang Song, Ji-Yun Seo, Yeon-Hee Bae, Ju-Young Kim, Hae-Young Lee, Whal Lee, Bon-Kwon Koo, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
المصدر: PLoS Biology, Vol 11, Iss 4, p e1001534 (2013)
بيانات النشر: Public Library of Science (PLoS), 2013.
سنة النشر: 2013
المجموعة: LCC:Biology (General)
مصطلحات موضوعية: Biology (General), QH301-705.5
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1544-9173
1545-7885
العلاقة: http://europepmc.org/articles/PMC3621676?pdf=renderTest; https://doaj.org/toc/1544-9173Test; https://doaj.org/toc/1545-7885Test
DOI: 10.1371/journal.pbio.1001534
الوصول الحر: https://doaj.org/article/68e84921bd3445a699c1313f9f359dcfTest
رقم الانضمام: edsdoj.68e84921bd3445a699c1313f9f359dcf
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:15449173
15457885
DOI:10.1371/journal.pbio.1001534