Rat Aortic Smooth Muscle Cells Cultured on Hydroxyapatite Differentiate into Osteoblast-Like Cells via BMP-2-SMAD-5 Pathway
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| 024 | 7 | 0 | |a 10.1007/s00223-015-9962-z |2 doi |
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| 245 | 0 | 0 | |a Rat Aortic Smooth Muscle Cells Cultured on Hydroxyapatite Differentiate into Osteoblast-Like Cells via BMP-2-SMAD-5 Pathway |h [Elektronische Daten] |c [Pranjal Nahar-Gohad, Neeraj Gohad, Chen-Chih Tsai, Rajendra Bordia, Naren Vyavahare] |
| 520 | 3 | |a Vascular calcification is an important pathological condition associated with increased risk of cardiovascular mortality. Hydroxyapatite (HA) found in such deposits is the same polymorph of calcium (Ca) found in bone, indicating calcification may involve mechanisms akin to bone formation. Vascular smooth muscle cells (Vsmcs) have been shown to undergo phenotypic change to osteoblast-like cells. However, the mechanisms underlying this phenotypic change are unclear, and whether the stimulus to become osteogenic is a result of loss of mineralization inhibitors or early mineral deposits is not known. Our aim in this study is to identify mechanisms and signal transduction pathways that cause differentiation of Vsmcs into osteoblast-like cells in the presence of HA. We first characterized vascular origin of Vsmcs by studying the expression of smooth muscle cell markers: myosin heavy chain and smooth muscle actin along with SM22α at both mRNA and protein levels. Vsmcs grown on HA exhibited progressive change in cellular morphology at 3-, 7-, and 14-day time points. Culturing of Vsmcs on HA disc resulted in decrease in media Ca levels and increased expression of Ca-sensing receptor (CaSR) on Vsmcs resulting inupregulation of intracellular CaSR signaling leading to increased BMP-2 secretion. BMP-2 pathway mediated differentiation of Vsmcs to osteoblast-like cells shown by expression of osteogenic markers like runt-related transcription factor 2, osteocalcin, and alkaline phosphatase at mRNA and protein levels. Blocking CaSR by NPS-2143 reduced BMP-2 secretion and blocking the BMP-2 pathway by LDN-193189, a BMP inhibitor, modulated expression of osteogenic markers confirming their role in osteogenesis of Vsmcs. | |
| 540 | |a Springer Science+Business Media New York, 2015 | ||
| 690 | 7 | |a Calcium-sensing receptor (CaSR) |2 nationallicence | |
| 690 | 7 | |a Hydroxyapatite (HA) |2 nationallicence | |
| 690 | 7 | |a Bone morphogenetic protein 2 (BMP-2) |2 nationallicence | |
| 690 | 7 | |a Vascular smooth muscle cells (Vsmcs) |2 nationallicence | |
| 690 | 7 | |a Osteogenic markers |2 nationallicence | |
| 690 | 7 | |a BMP-2 inhibitor LDN |2 nationallicence | |
| 690 | 7 | |a SMAD-5: Sma- and Mad-related protein 5 |2 nationallicence | |
| 690 | 7 | |a VSMCs : Vascular smooth muscle cells |2 nationallicence | |
| 690 | 7 | |a GAPDH : Glyceraldehyde 3-phosphate dehydrogenase |2 nationallicence | |
| 690 | 7 | |a SMA : Alpha smooth muscle actin |2 nationallicence | |
| 690 | 7 | |a MHC : Myosin heavy chain |2 nationallicence | |
| 690 | 7 | |a BMP-2 : Bone morphogenetic protein 2 |2 nationallicence | |
| 690 | 7 | |a SMAD-5 : Sma- and Mad-related protein 5 |2 nationallicence | |
| 690 | 7 | |a Col2a1 : Collagen type II alpha 1 |2 nationallicence | |
| 690 | 7 | |a RUNX2 : Runt-related transcription factor 2 |2 nationallicence | |
| 690 | 7 | |a ALP : Alkaline phosphatase |2 nationallicence | |
| 690 | 7 | |a DAPI : 4′,6-Diamidino-2-phenylindole, dihydrochloride |2 nationallicence | |
| 690 | 7 | |a HA : Hydroxyapatite |2 nationallicence | |
| 690 | 7 | |a MGP : Matrix-gla protein |2 nationallicence | |
| 700 | 1 | |a Nahar-Gohad |D Pranjal |u Department of Bioengineering, Clemson University, 501 Rhodes Research Center, 29634, Clemson, SC, USA |4 aut | |
| 700 | 1 | |a Gohad |D Neeraj |u Department of Biological Sciences, Clemson University, 132 Long Hall, 29634, Clemson, SC, USA |4 aut | |
| 700 | 1 | |a Tsai |D Chen-Chih |u Department of Material Sciences, Clemson University, 161 Sirrine Hall, 29634, Clemson, SC, USA |4 aut | |
| 700 | 1 | |a Bordia |D Rajendra |u Department of Material Sciences, Clemson University, 161 Sirrine Hall, 29634, Clemson, SC, USA |4 aut | |
| 700 | 1 | |a Vyavahare |D Naren |u Department of Bioengineering, Clemson University, 501 Rhodes Research Center, 29634, Clemson, SC, USA |4 aut | |
| 773 | 0 | |t Calcified Tissue International |d Springer US; http://www.springer-ny.com |g 96/4(2015-04-01), 359-369 |x 0171-967X |q 96:4<359 |1 2015 |2 96 |o 223 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00223-015-9962-z |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00223-015-9962-z |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Nahar-Gohad |D Pranjal |u Department of Bioengineering, Clemson University, 501 Rhodes Research Center, 29634, Clemson, SC, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Gohad |D Neeraj |u Department of Biological Sciences, Clemson University, 132 Long Hall, 29634, Clemson, SC, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Tsai |D Chen-Chih |u Department of Material Sciences, Clemson University, 161 Sirrine Hall, 29634, Clemson, SC, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bordia |D Rajendra |u Department of Material Sciences, Clemson University, 161 Sirrine Hall, 29634, Clemson, SC, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Vyavahare |D Naren |u Department of Bioengineering, Clemson University, 501 Rhodes Research Center, 29634, Clemson, SC, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Calcified Tissue International |d Springer US; http://www.springer-ny.com |g 96/4(2015-04-01), 359-369 |x 0171-967X |q 96:4<359 |1 2015 |2 96 |o 223 | ||