Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference

Publication date: June 2018Source: Genes &Diseases, Volume 5, Issue 2Author(s): Shujuan Yan, Ruyi Zhang, Ke Wu, Jing Cui, Shifeng Huang, Xiaojuan Ji, Liping An, Chengfu Yuan, Cheng Gong, Linghuan Zhang, Wei Liu, Yixiao Feng, Bo Zhang, Zhengyu Dai, Yi Shen, Xi Wang, Wenping Luo, Bo Liu, Rex C. Haydon, Michael J. LeeAbstractMesenchymal stem cells (MSCs) are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic, chondrogenic and adipogenic lineages. We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood. Here, we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs. Using two different siRNA bioinformatic prediction programs, we design five siRNAs targeting mouse BMP9 (or simB9), which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors. We demonstrate that two of the five siRNAs, simB9-4 and simB9-7, exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs. Furthermore, simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers, matrix mineralization and ectopic bone formation from MSCs. Thus, our findings demonstrate the important ro...
Source: Genes and Diseases - Category: Genetics & Stem Cells Source Type: research

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This article will discuss therapeutic strategies for AdV infection in the pediatrics transplant recipient. Recent findings Currently, there is no FDA approved antiviral therapy for AdV infection. Accordingly, the primary initial therapy would be decreasing immunosuppression, whenever possible. Cidofovir (CDV) is an antiviral drug whose use has been associated with significant reductions of AdV viral load and, in some series improved survival in recipients of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT). However, its use is also associated with significant toxicity. Brincidofovir (BCV) is a ...
Source: Current Opinion in Organ Transplantation - Category: Surgery Tags: INFECTIOUS COMPLICATIONS IN TRANSPLANTATION: Edited by Shimon Kusne Source Type: research
ConclusionsOur results indicate that the proposed in vitro model is suitable for the study of the structural defects of desmin-mutated cardiomyocytes.
Source: Archives of Cardiovascular Diseases Supplements - Category: Cardiology Source Type: research
Publication date: 8 May 2018Source: Stem Cell Reports, Volume 10, Issue 5Author(s): Satoshi Watanabe, Mito Kanatsu-Shinohara, Narumi Ogonuki, Shogo Matoba, Atsuo Ogura, Takashi ShinoharaSummaryAdeno-associated virus (AAV) penetrates the blood-brain barrier, but it is unknown whether AAV penetrates other tight junctions. Genetic manipulation of testis has been hampered by the basement membrane of seminiferous tubules and the blood-testis barrier (BTB), which forms between Sertoli cells and divides the tubules into basal and adluminal compartments. Here, we demonstrate in vivo genetic manipulation of spermatogonial stem...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
ConclusionThe study demonstrates the safety and feasibility of pre-emptively manufacturing peptide pulsed ADV-specific cells for high-risk pediatric patients after transplantation and provides early evidence of clinical efficacy.
Source: Cytotherapy - Category: Cytology Source Type: research
ConclusionsOur study shows a high diversity in HAdV DNA pol sequences in clinical species C HAdV and provides a comprehensive mapping of its natural polymorphism. These data will contribute to the interpretation of HAdV DNA pol mutations selected in patients receiving antiviral treatments.
Source: Antiviral Therapy - Category: Virology Source Type: research
Publication date: April 2018Source: Current Opinion in Virology, Volume 29Author(s): Sasirekha Ramani, Sue E Crawford, Sarah E Blutt, Mary K EstesStudies of human infectious diseases have been limited by the paucity of functional models that mimic normal human physiology and pathophysiology. Recent advances in the development of multicellular, physiologically active organotypic cultures produced from embryonic and pluripotent stem cells, as well as from stem cells isolated from biopsies and surgical specimens are allowing unprecedented new studies and discoveries about host–microbe interactions. Here, we summarize re...
Source: Current Opinion in Virology - Category: Virology Source Type: research
Publication date: 1 October 2018Source: Physiology &Behavior, Volume 194Author(s): Hawley E. Kunz, Guillaume Spielmann, Nadia H. Agha, Daniel P. O'Connor, Catherine M. Bollard, Richard J. SimpsonAbstractAdoptive transfer of virus-specific T-cells (VSTs) effectively treats viral infections following allogeneic hematopoietic stem cell transplantation (alloHSCT), but logistical difficulties have limited widespread availability of VSTs as a post-transplant therapeutic. A single exercise bout mobilizes VSTs specific for latent herpesviruses (i.e. CMV and EBV) to peripheral blood and augments their ex vivo expansion. We inve...
Source: Physiology and Behavior - Category: Physiology Source Type: research
Publication date: June 2018Source: Genes &Diseases, Volume 5, Issue 2Author(s): Shujuan Yan, Ruyi Zhang, Ke Wu, Jing Cui, Shifeng Huang, Xiaojuan Ji, Liping An, Chengfu Yuan, Cheng Gong, Linghuan Zhang, Wei Liu, Yixiao Feng, Bo Zhang, Zhengyu Dai, Yi Shen, Xi Wang, Wenping Luo, Bo Liu, Rex C. Haydon, Michael J. LeeAbstractMesenchymal stem cells (MSCs) are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic, chondrogenic and adipogenic lineages. We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact mo...
Source: Genes and Diseases - Category: Genetics & Stem Cells Source Type: research
ConclusionsOur results indicate that the proposed in vitro model is suitable for the study of the structural defects of desmin-mutated cardiomyocytes.
Source: Archives of Cardiovascular Diseases Supplements - Category: Cardiology Source Type: research
Publication date: 8 May 2018Source: Stem Cell Reports, Volume 10, Issue 5Author(s): Satoshi Watanabe, Mito Kanatsu-Shinohara, Narumi Ogonuki, Shogo Matoba, Atsuo Ogura, Takashi ShinoharaSummaryAdeno-associated virus (AAV) penetrates the blood-brain barrier, but it is unknown whether AAV penetrates other tight junctions. Genetic manipulation of testis has been hampered by the basement membrane of seminiferous tubules and the blood-testis barrier (BTB), which forms between Sertoli cells and divides the tubules into basal and adluminal compartments. Here, we demonstrate in vivo genetic manipulation of spermatogonial stem...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
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