Local administration of nuclear factor of activated T cells (NFAT) c1 inhibitor to suppress early resorption and inflammation induced by bone morphogenetic protein-2

2018 ◽  
Vol 106 (5) ◽  
pp. 1299-1310 ◽  
Author(s):  
Ri Youn Kim ◽  
Yeju Seong ◽  
Tae Hyung Cho ◽  
Beomseok Lee ◽  
In Sook Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Local Administration ◽  
Nuclear Factor ◽  
C1 Inhibitor ◽  
Activated T Cells ◽  
Morphogenetic Protein

Effects of strontium-modified calcium phosphate cement combined with bone morphogenetic protein-2 on osteoporotic bone defects healing in rats

2018 ◽  
Vol 33 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Zhoushan Tao ◽  
Wanshu Zhou ◽  
Yunyun Jiang ◽  
Xingjin Wu ◽  
Zhujun Xu ◽  
...  
Keyword(s):  
Single Dose ◽  
Calcium Phosphate ◽  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Calcium Phosphate Cement ◽  
Bone Morphogenetic Protein 2 ◽  
Local Administration ◽  
Ovx Rats ◽  
Local Bone ◽  
Morphogenetic Protein

The objective of the present study was to incorporate strontium into calcium phosphate cement combined with a lower single-dose local administration of bone morphogenetic protein-2 to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, strontium-modified calcium phosphate cement was prepared by mixing sieved granules of calcium phosphate cement and 5% SrCO3 for medical use, and then strontium-modified calcium phosphate cement with dripped bone morphogenetic protein-2 solution (5 µg) was implanted into the defect of OVX rats until death at eight weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that a lower single-dose local administration of bone morphogenetic protein-2 combined local usage of strontium-modified calcium phosphate cement can increase the healing of defects in OVX rats. Furthermore, treatments with single-dose local administration of bone morphogenetic protein-2 and strontium-modified calcium phosphate cement showed a stronger effect on accelerating the local bone formation than calcium phosphate cement and strontium-modified calcium phosphate cement used alone. The results from our study demonstrate that combination of a lower single-dose local administration of bone morphogenetic protein-2 and strontium-modified calcium phosphate cement had an additive effect on local bone formation in osteoporosis rats.

Abstract 627: Regulation of Nuclear Factor of Activated T Cells by BMP-Binding Endothelial Regulator Signaling

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Pamela P Lockyer ◽  
Hua Mao ◽  
Xi Li ◽  
Xinchun Pi
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Transcriptional Activity ◽  
Ldl Receptor ◽  
Bmp Signaling ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Morphogenetic Protein ◽  
Endothelial Integrity

Dysfunction of the vascular endothelium results in various cardiovascular, circulatory and blood diseases and exemplifies the importance of endothelial integrity. BMP-binding endothelial regulator (BMPER), a well recognized extracellular modulator of Bone morphogenetic protein (BMP) signaling, has been identified as a vital component in the vascular response to stress. Microarray analysis revealed nuclear factor of activated T cells (NFAT) as one of the genes found to be most highly upregulated by BMPER treatment in mouse endothelial cells (MECs), as well as many genes with NFAT consensus binding sites. Therefore we hypothesize that BMPER is an important regulator of NFAT transcriptional activity. Initially we have investigated the effect of BMPER on NFATc1 activation with MECs and human primary endothelial cells. Our data show that the translocation of NFATc1 from the cytoplasm to the nucleus following BMPER treatment, determined by immunofluorescent analysis. By using the nuclear fractionation assays, we observed the similar result that the translocation of NFATc1 to the nucleus of HUVECs took place after 30 minutes of BMPER treatment. Next, we wanted to determine whether the increased NFATc1 protein level in nucleus results in the enhanced transcriptional activity. Indeed, when HUVECs are treated with BMPER and then analyzed with luciferase reporter assay, a 1.5-fold significant increase in NFAT activity over baseline was observed. Our previous data demonstrate that LDL receptor related protein (LRP1) interacts with BMPER and regulates BMPER’s activity through endocytosis in endothelial cells. Interesting, we observe that LRP1 also interacts with NF45, the 45-kDa subunit of NFAT protein. It strongly suggests that BMPER positively regulates NFAT activity through LRP1. This novel signaling pathway indicates that BMPER may acts as a new ligand and exhibits BMP-independent activity in endothelial cells and therefore contribute to the regulation of vascular homeostasis.

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