Bone Morphogenetic Protein 4 Contributes to the Maintenance of Primitive Cord Blood Hematopoietic Progenitors in an Ex Vivo Stroma-Noncontact Co-Culture System

2006 ◽  
Vol 15 (6) ◽  
pp. 805-813 ◽  
Author(s):  
Jonathon F. Hutton ◽  
Vladislav Rozenkov ◽  
Fiona S.L. Khor ◽  
Richard J. D'Andrea ◽  
Ian D. Lewis
2003 ◽  
Vol 23 (13) ◽  
pp. 4627-4636 ◽  
Author(s):  
Mari Kiyono ◽  
Masabumi Shibuya

ABSTRACT Programmed capillary regression is essential for development, but little is known about the mechanism behind this phenomenon. In this study, we characterized the molecular determinants of capillary regression utilizing the pupillary membrane (PM) in the newborn rat's eye. We observed in the 1-day-culture system that apoptotic endothelial cells decrease in number with the addition of a natural antagonist, Noggin, strongly suggesting the involvement of the bone morphogenetic protein (BMP) family in PM regression. In addition, the lens-conditioned medium (Lens-CM) induced apoptosis of HUVE cells and inhibited endothelial tubulogenesis, which were completely blocked by both Noggin and the BMP4-specific neutralizing antibody. Activation of BMP4 pathway in endothelial cells was confirmed by both the up-regulation of Msx genes correlated with apoptosis and the translocation of Smad1 into the nucleus. We showed a transient expression of BMP4 in Lens-CM by immunoprecipitation assay. Furthermore, the transcorneal injection of BMP4 in rats enhanced the apoptosis of PMs, while that of Noggin attenuated it. These results indicate that BMP4 pathways play pivotal roles in capillary regression in a paracrine manner between lens and PMs.


Blood ◽  
2001 ◽  
Vol 98 (2) ◽  
pp. 335-342 ◽  
Author(s):  
Fei Li ◽  
Shijiang Lu ◽  
Loyda Vida ◽  
James A. Thomson ◽  
George R. Honig

A cell culture system consisting of mouse S17 stromal cells supplemented with cytokines was developed for hematopoietic differentiation of rhesus monkey embryonic stem (ES) cells. The differentiated colonies that formed contained clusters of hematopoietic-like cells, as well as structures similar in appearance to embryonic blood islands. When this culture system was supplemented with bone morphogenetic protein 4 (BMP-4), the numbers of primary hematopoietic clusters increased by an average of 15 fold. The primary hematopoietic clusters containing clonogenic precursors (expandable hematopoietic clusters) increased by 18 fold. Immunofluorescence analysis showed that a substantial percentage of the hematopoietic-like cells were CD34+, with morphologic features of undifferentiated blast cells. Enrichment of the CD34+ cells was associated with enhanced stromal-dependent, cytokine-driven formation of cobblestone colonies on secondary plating. The hematopoietic identity of the precursors was further indicated by their expression of genes associated with hematopoietic differentiation, as well as morphologic assessments that showed erythroid and myeloid lineages among the progeny cells. In addition, reverse transcriptase–polymerase chain reaction analysis of BMP-4–treated rhesus monkey ES cells demonstrated an up-regulation of early-expressed genes responsible for embryonic hematopoiesis and angiogenesis during the first 7 days of culture. These observations suggest that embryonic mesoderm regulatory protein may mimic physiologic signals that are required for the onset of embryonic hematopoiesis and stem cell formation in rhesus monkey ES cells.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lovorka Grgurevic ◽  
Ruder Novak ◽  
Grgur Salai ◽  
Vladimir Trkulja ◽  
Lejla Ferhatovic Hamzic ◽  
...  

Abstract Background This study was conducted in order to explore the effects of orthodontic tooth movement (OTM) on the changes of salivary proteome. This prospective observational pilot study recruited 12 healthy teenage boys with malocclusion treated with a fixed orthodontic appliance and 6 appropriate control participants. Saliva samples were collected a day before and at 0, 2, 7, and 30 days after initialization of treatment, corresponding to the initial, lag, and post-lag phases of OTM. Pooled samples were analyzed by liquid chromatography-mass spectrometry, ELISA, and Western blotting. To date, there is no published data on the presence of BMP molecules or their antagonists in the saliva or in the gingival cervical fluid related to orthodontic conditions. Results A total of 198 identified saliva proteins were classified based on their functional characteristics. Proteins involved in bone remodeling were observed exclusively 30 days post appliance placement, including bone morphogenetic protein 4 (BMP4), a BMP antagonist BMP-binding endothelial regulator, insulin-like growth factor-binding protein 3, cytoskeleton-associated protein 4, and fibroblast growth factor 5. Based on the analysis of protein interactions, BMP4 was found to have a central position in this OTM-related protein network. Conclusions The placement of a fixed orthodontic appliance induced occurrence of proteins involved in bone remodeling in the saliva at a time corresponding to the post-lag period of OTM. Limitations of this study include a relatively small sample size, limited time of monitoring patients, and the lack of interindividual variability assessment.


1994 ◽  
Vol 277 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Seiichi Hirota ◽  
Kunio Takaoka ◽  
Jun Hashimoto ◽  
Takanobu Nakase ◽  
Teiji Takemura ◽  
...  

2002 ◽  
Vol 245 (2) ◽  
pp. 291-303 ◽  
Author(s):  
Yuji Nakajima ◽  
Toshiyuki Yamagishi ◽  
Katsumi Ando ◽  
Hiroaki Nakamura

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