Abstract：
:Mesenchymal stromal progenitor cells (MSCs) are multipotent progenitors that can be isolated from numerous tissues. MSCs can undergo osteogenic differentiation under proper stimuli. We have recently demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most osteogenic BMPs. As one of the least studied BMPs, BMP9 has been shown to regulate angiogenesis in endothelial cells. However, it is unclear whether BMP9-regulated angiogenic signaling plays any important role in the BMP9-initiated osteogenic pathway in MSCs. Here, we investigate the functional role of hypoxia-inducible factor 1α (HIF1α)-mediated angiogenic signaling in BMP9-regulated osteogenic differentiation of MSCs. We find that BMP9 induces HIF1α expression in MSCs through Smad1/5/8 signaling. Exogenous expression of HIF1α potentiates BMP9-induced osteogenic differentiation of MSCs both in vitro and in vivo. siRNA-mediated silencing of HIF1α or HIF1α inhibitor CAY10585 profoundly blunts BMP9-induced osteogenic signaling in MSCs. HIF1α expression regulated by cobalt-induced hypoxia also recapitulates the synergistic effect between HIF1α and BMP9 in osteogenic differentiation. Mechanistically, HIF1α is shown to exert its synergistic effect with BMP9 by inducing both angiogenic signaling and osteogenic signaling in MSCs. Thus, our findings should not only expand our understanding of the molecular basis behind BMP9-regulated osteoblastic lineage-specific differentiation, but also provide an opportunity to harness the BMP9-induced synergy between osteogenic and angiogenic signaling pathways in regenerative medicine.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Hu N,Jiang D,Huang E,Liu X,Li R,Liang X,Kim SH,Chen X,Gao JL,Zhang H,Zhang W,Kong YH,Zhang J,Wang J,Shui W,Luo X,Liu B,Cui J,Rogers MR,Shen J,Zhao C,Wang N,Wu N,Luu HH,Haydon RC,He TC,Huang Wdoi
10.1242/jcs.114231subject
Has Abstractpub_date
2013-01-15 00:00:00pages
532-41issue
Pt 2eissn
0021-9533issn
1477-9137pii
jcs.114231journal_volume
126pub_type
杂志文章abstract：:Low doses of the muscarinic agonist pilocarpine (0.1-1 microM) and the beta-adrenergic agonist isoproterenol (0.5-4 nM) stimulate a minor regulated secretory pathway for salivary proteins in rat parotid lobules. Newly synthesized proteins (labeled biosynthetically) are selectively discharged, and they are secreted in ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:Axonemal dyneins are multisubunit molecular motors that provide the driving force for flagellar motility. Dynein light chain 1 (LC1) has been well studied in Chlamydomonas reinhardtii and is unique among all dynein components as the only protein known to bind directly to the catalytic motor domain of the dynein heavy ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.004846
更新日期：2007-05-01 00:00:00
abstract：:A major challenge in biology is to understand how genetic information is interpreted to direct the formation of specialized tissues within a multicellular organism. During differentiation, changes in chromatin structure and nuclear organization establish heritable patterns of gene expression in response to signals. Ep...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01390
更新日期：2004-09-01 00:00:00
abstract：:In contrast to the highly dynamic actin cytoskeleton in non-muscle cells, actin filaments in muscle sarcomeres are thought to be relatively stable and undergo dynamics only at their ends. However, many proteins that promote rapid actin dynamics are also expressed in striated muscles. We show that a subset of actin fil...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.046805
更新日期：2009-06-15 00:00:00
abstract：:Cell migration makes a fundamental contribution to both normal physiology and disease pathogenesis. Integrin engagement with extracellular ligands spatially controls, via the cyclical activation and deactivation of the small GTPase Rac1, the dynamic membrane protrusion and cytoskeletal reorganization events that are r...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.121988
更新日期：2013-09-15 00:00:00
abstract：:Eggs of Urechis caupo are surrounded by a congruent to 0.9 micrometer thick egg envelope and, attached to that, a peripheral jelly layer about 3 micrometers thick. Before fertilization, the sperm undergoes the acrosome reaction and binds to the egg envelope. As part of a study of the induction of the acrosome reaction...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1985-03-01 00:00:00
abstract：:The interaction of promastigotes of the protozoan parasite Leishmania tropica with mouse peritoneal macrophages in vitro was studied by scanning electron microscopy. Motile promastigotes attached to host cells by their flagellar tips to which the macrophages responded by producing rather closely fitting lamellar sheat...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-10-01 00:00:00
abstract：:NF-kappaB plays a central role in mediating pathogen and cytokine-stimulated gene transcription. NF-kappaB repressing factor (NRF) has been shown to interact with specific negative regulatory DNA elements (NRE) to mediate transcriptional repression by inhibition of the NF-kappaB activity at certain promoters. mRNA abl...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01129
更新日期：2004-07-15 00:00:00
abstract：:The Schizosaccaromyces pombe protein Flp1p belongs to a conserved family of serine-threonine-phosphatases. The founding member of this family, Saccharomyces cerevisiae Cdc14p, is required for inactivation of mitotic CDKs and reversal of CDK mediated phosphorylation at the end of mitosis, thereby bringing about the M-G...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01107
更新日期：2004-05-15 00:00:00
abstract：:Every two years, the French Society for Cell Biology (SBCF) organises an international meeting called 'Imaging the Cell'. This year, the 8th edition was held on 24-26 June 2015 at University of Bordeaux Campus Victoire in the city of Bordeaux, France, a UNESCO World Heritage site. Over the course of three days, the me...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.180042
更新日期：2015-11-01 00:00:00
abstract：:The invasiveness of cells is correlated with the presence of dynamic actin-rich membrane structures called invadopodia, which are membrane protrusions that are associated with localized polymerization of sub-membrane actin filaments. Similar to focal adhesions and podosomes, invadopodia are cell-matrix adhesion sites....
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.052704
更新日期：2009-09-01 00:00:00
abstract：:Hepatocyte growth factor, also known as scatter factor, is a pleiotropic cytokine, which stimulates cell motility, invasion, proliferation, survival and morphogenesis, and induces the expression of specific genes by activating its receptor tyrosine kinase. In this work we have isolated, characterized and used as agoni...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：:The ret finger protein (rfp) is a member of the B-box zinc finger gene family many of which may function in growth regulation and in the appropriate context become oncogenic. Members of this family are nuclear proteins that possess a characteristic tripartite motif consisting of the RING and B-box zinc binding domains...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:In the eukaryotic cell, a protein quality control process termed endoplasmic reticulum-associated degradation (ERAD) rids the ER of aberrant proteins and unassembled components of protein complexes that fail to reach a transport-competent state. To identify novel genes required for ERAD, we devised a rapid immunoassay...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00439
更新日期：2003-06-01 00:00:00
abstract：:The roles of P21-activated kinase (PAK) in the regulation of axon outgrowth downstream of extracellular matrix (ECM) proteins are poorly understood. Here we show that PAK1-3 and PIX are expressed in the developing spinal cord and differentially localize to point contacts and filopodial tips within motile growth cones....
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.112607
更新日期：2013-03-01 00:00:00
abstract：:When tumour cells are fused with normal ones, malignancy is suppressed. It has been shown that this suppression is associated with the imposition on the hybrid cell of the terminal differentiation programme of the normal parent cell. We report here the consequences of imposing the synthesis of keratin 1 and keratin 10...
journal_title：Journal of cell science
pub_type：
doi：
更新日期：1996-09-01 00:00:00
abstract：:Fine-tuning of NMDA glutamatergic receptor signalling strategically controls crucial brain functions. This process depends on several ligands and modulators, one of which unexpectedly includes the serine protease tissue-type plasminogen activator (tPA). In vitro, tPA increases NMDA-receptor-mediated calcium influx by ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03354
更新日期：2007-02-15 00:00:00
abstract：:Syntaxin 1C (STX1C), produced by alternative splicing of the stx1A gene, is a soluble syntaxin lacking a SNARE domain and a transmembrane domain. It is unclear how soluble syntaxin can control intracellular membrane trafficking. We found that STX1C affected microtubule (MT) dynamics through its tubulin-binding domain ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.081943
更新日期：2012-02-15 00:00:00
abstract：:We have previously shown that Xenopus oocytes, eggs, and early embryos contain lamins LII and LIII, and that portions of each are associated with distinct egg vesicle populations. We now report that a lamin similar or identical to the B-type lamin LI is also present in oocyte nuclei and in egg extracts. We have quanti...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:The formation of complex dendritic arbors is crucial for the assembly of functional networks as abnormal dendrite formation underlies several neurodevelopmental and psychiatric disorders. Many extracellular factors have been postulated as regulators of dendritic growth. Wnt proteins play a critical role in neuronal de...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.216101
更新日期：2018-07-09 00:00:00
abstract：:Mesenchymal stem cells (MSCs) are among the most promising and suitable stem cell types for vascular tissue engineering. Substantial effort has been made to differentiate MSCs towards vascular cell phenotypes, including endothelial cells and smooth muscle cells (SMCs). The microenvironment of vascular cells not only c...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.167783
更新日期：2015-07-15 00:00:00
abstract：:Centaurin-alpha(1) is a phosphatidylinositol 3,4,5-trisphosphate binding protein as well as a GTPase activating protein (GAP) for the ADP-ribosylation factor (ARF) family of small GTPases. To further understand its cellular function, we screened a rat brain cDNA library using centaurin-alpha(1) as bait to identify cen...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02369
更新日期：2005-06-01 00:00:00
abstract：:Using a series of chimeric and truncated N-acetylglucosaminyltransferase I (NAGT I) molecules we have shown that part of the lumenal stalk region is both necessary and sufficient for kin recognition of mannosidase II and retention in the Golgi stack. The membrane-spanning domain was not required for retention, but rep...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:To examine the internal structure of chromatin fibers, we have developed procedures for partial denaturation of small chromatin fragments (8-30 nucleosomes) from chicken erythrocytes. Electron micrographs of samples prepared under conditions that cause nucleosome dissociation show rods and loops projecting from short ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-06-01 00:00:00
abstract：:Tritiated-thymidine autoradiography was used to follow the progress of cells through meiosis in male P. cinereus at 20 degrees C. Spermatocytes spend 7 days in leptotene, 5 days in zygotene and 3 days in pachytene before entering the diffuse stage. Diffuse lasts for 8 days and is followed by a diplotene of 2 days. Fir...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-08-01 00:00:00
abstract：:The fractionation of human liver mitochondria into inner membrane, outer membrane and matrix material is reported. Compared with rat, human liver mitochondria are more fragile. Fractionation can be achieved in only 2 steps, a digitonin treatment for removal of the outer membrane and centrifugation of the inner membran...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:Evidence from various systems suggests that either asters or the midzone of the mitotic spindle are the predominant determinants of cleavage plane position. Disrupting spindle midzone formation in the one-cell Caenorhabditis elegans embryo, such as by using mutants of the centralspindlin component ZEN-4, prevents comp...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03447
更新日期：2007-05-15 00:00:00
abstract：:Adult newt cardiomyocytes, in contrast to their mammalian counterparts, can proliferate after injury and contribute to the functional regeneration of the heart. In order to understand the mechanisms underlying this plasticity we performed longitudinal studies on single cardiomyocytes in culture. We find that the major...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00698
更新日期：2003-10-01 00:00:00
abstract：:Successful implantation requires the synchronization of viable embryonic development with endometrial receptivity. The mechanisms allowing for the initiation of crosstalk between the embryo and the endometrium remain elusive; however, recent studies have revealed that there are alterations in endometrial microRNAs (mi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.164004
更新日期：2015-02-15 00:00:00
abstract：:Increases in RNA, protein and cell size were determined cytophotometrically during the cell division cycle of Tetrahymena. For these parameters different patterns were found. RNA accumulates slowly during G1 period and faster during macronuclear S. This agrees with the changing uridine incorporation rate which is at l...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-06-01 00:00:00
