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https://www.readbyqxmd.com/read/28335084/identification-of-new-bmp6-pro-peptide-mutations-in-patients-with-iron-overload
#1
Chiara Piubelli, Annalisa Castagna, Giacomo Marchi, Monica Rizzi, Fabiana Busti, Sadaf Badar, Monia Marchetti, Marco De Gobbi, Antonella Roetto, Luciano Xumerle, Eda Suku, Alejandro Giorgetti, Massimo Delledonne, Oliviero Olivieri, Domenico Girelli
Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least 5 different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Nevertheless, patients with an HH-like phenotype that remains completely/partially unexplained despite extensive sequencing of known genes are not infrequently seen at referral centers, suggesting a role of still unknown genetic factors. A compelling candidate is Bone Morphogenetic Protein 6 (BMP6), which acts as a major activator of the BMP-SMAD signaling pathway, ultimately leading to the upregulation of hepcidin gene transcription...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28322831/chemical-inhibitors-of-c-met-receptor-tyrosine-kinase-stimulate-osteoblast-differentiation-and-bone-regeneration
#2
Jung-Woo Kim, Mi Nam Lee, Byung-Chul Jeong, Sin-Hye Oh, Min-Suk Kook, Jeong-Tae Koh
The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been recently introduced to negatively regulate bone morphogenetic protein (BMP)-induced osteogenesis. However, the effect of chemical inhibitors of c-Met receptor on osteoblast differentiation process has not been examined, especially the applicability of c-Met chemical inhibitors on in vivo bone regeneration. In this study, we demonstrated that chemical inhibitors of c-Met receptor tyrosine kinase, SYN1143 and SGX523, could potentiate the differentiation of precursor cells to osteoblasts and stimulate regeneration in calvarial bone defects of mice...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28315766/bone-morphogenetic-protein-4-is-overexpressed-in-and-promotes-migration-and-invasion-of-drug-resistant-cancer-cells
#3
Kairui Zhou, Xiaoli Shi, Jinling Huo, Weihua Liu, Dongxiao Yang, Tengjiao Yang, Tiantian Qin, Cong Wang
Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-β superfamily, has broad biological activities in cell proliferation and cartilage differentiation and is also able to induce migration and invasion. Herein, we investigated the role of BMP4 in the regulation of metastasis in paclitaxel-resistant human esophageal carcinoma EC109 cells (EC109/Taxol) and docetaxel-resistant human gastric cancer MGC803 cells (MGC/Doc)...
March 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28299802/bmp-and-notch-interaction-in-crc-subtypes
#4
Shazia Irshad, Mukesh Bansal, Paolo Guarnieri, Hayley Davis, Ayman Al Haj Zen, Brygida Baran, Claudia Maria Assunta Pinna, Haseeb Rahman, Sujata Biswas, Chiara Bardella, Rosemary Jeffery, Lai Mun Wang, James Edward East, Annabelle Lewis, Ian Tomlinson, Simon John Leedham
The functional role of Bone Morphogenetic Protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes...
March 15, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28265470/combination-of-interleukin-27-and-microrna-for-enhancing-expression-of-anti-inflammatory-and-proosteogenic-genes
#5
Manoel Figueiredo Neto, Marxa L Figueiredo
Remission of inflammation has become an achievable goal in inflammatory or rheumatoid arthritis (RA); however, bone erosion continues in many patients. Interleukin- (IL-) 27 regulates immune and bone cell balance and also suppresses activities of several inflammatory cell types in RA. Despite its promise, challenges to clinical translation of IL-27 have been its partial effects in vivo. Due to their ability to modulate plasticity of bone and immune cell differentiation, we examined the potential for several microRNA (miR) candidates in enhancing the effects of IL-27...
2017: Arthritis
https://www.readbyqxmd.com/read/28259395/short-communication-tryptic-%C3%AE-casein-hydrolysate-modulates-enteric-nervous-system-development-in-primary-culture
#6
F Cossais, I Clawin-Rädecker, P C Lorenzen, M Klempt
The intestinal tract of the newborn is particularly sensitive to gastrointestinal disorders, such as infantile diarrhea or necrotizing colitis. Perinatal development of the gut also encompasses the maturation of the enteric nervous system (ENS), a main regulator of intestinal motility and barrier functions. It was recently shown that ENS maturation can be enhanced by nutritional factors to improve intestinal maturation. Bioactivity of milk proteins is often latent, requiring the release of bioactive peptides from inactive native proteins...
March 2, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28229387/the-effects-of-cerium-valence-states-at-cerium-oxide-coatings-on-the-responses-of-bone-mesenchymal-stem-cells-and-macrophages
#7
Mingyu You, Kai Li, Youtao Xie, Liping Huang, Xuebin Zheng
Ideal orthopedic coatings should trigger good osteogenic response and limited inflammatory response. The cerium valence states in ceria are associated with their anti-oxidative activity and anti-inflammatory property. In the study, we prepared two kinds of plasma sprayed CeO2 coatings with different Ce(4+) concentrations to investigate the effects of Ce valence states on the response of bone mesenchymal stem cells (BMSCs) and macrophage RAW264.7. Both the coatings (CeO2-A and CeO2-B) were characterized via XRD, SEM, and X-ray photoelectron spectroscopy...
February 22, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28202676/harnessing-the-bmp-signaling-pathway-to-control-the-formation-of-cancer-stem-cells-by-effects-on-epithelial-to-mesenchymal-transition
#8
REVIEW
Ashish Bosukonda, William D Carlson
Cancer stem cells (CSCs) persist in tumors as a distinct population and may be causative in metastasis and relapse. CSC-rich tumors are associated with higher rates of metastasis and poor patient prognosis. Targeting CSCs therapeutically is challenging, since they seem to be resistant to standard chemotherapy. We have shown that a novel peptide agonist of bone morphogenetic protein (BMP) signaling, P123, is capable of inhibiting the growth of primary tumor cells by interacting with type I receptors selectively [activin receptor-like kinase 2 (ALK2) and ALK3, but not ALK6] and type II BMP receptors, activating SMAD 1/5/8 signaling and controlling the cell cycle pathway...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28188849/endocytosis-contributes-to-bmp2-induced-smad-signalling-and-neuronal-growth
#9
Shane V Hegarty, Aideen M Sullivan, Gerard W O'Keeffe
Bone morphogenetic protein 2 (BMP2) is a neurotrophic factor which induces the growth of midbrain dopaminergic (DA) neurons in vitro and in vivo, and its neurotrophic effects have been shown to be dependent on activation of BMP receptors (BMPRs) and Smad 1/5/8 signalling. However, the precise intracellular cascades that regulate BMP2-BMPR-Smad-signalling-induced neurite growth remain unknown. Endocytosis has been shown to regulate Smad 1/5/8 signalling and differentiation induced by BMPs. However, these studies were carried out in non-neural cells...
March 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28182872/enhanced-critical-size-calvarial-bone-healing-by-ascs-engineered-with-cre-loxp-based-hybrid-baculovirus
#10
Shih-Chun Lo, Kuei-Chang Li, Yu-Han Chang, Mu-Nung Hsu, Li-Yu Sung, Truong Anh Vu, Yu-Chen Hu
Calvarial bone repair remains challenging for adults. Although adipose-derived stem cells (ASCs) hold promise to heal bone defects, use of ASCs for critical-size calvarial bone repair is ineffective. Stromal cell-derived factor 1 (SDF-1) is a chemokine capable of triggering stem cell migration. Although recombinant SDF-1 protein is co-delivered with other molecules including BMP-2 to facilitate calvarial bone repair, these approaches did not yield satisfactory healing. This study aimed to exploit a newly developed Cre/loxP-based hybrid baculovirus for efficient gene delivery and prolonged transgene expression in ASCs...
January 30, 2017: Biomaterials
https://www.readbyqxmd.com/read/28155178/tumor-necrosis-factor-%C3%AE-and-transforming-growth-factor-%C3%AE-1-facilitate-differentiation-and-proliferation-of-tendon-derived-stem-cells-in-vitro
#11
Peilin Han, Qingbo Cui, Shulong Yang, Hao Wang, Peng Gao, Zhaozhu Li
OBJECTIVES: To investigate the effects of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) on the proliferation and differentiation of tendon-derived stem cells (TDSC). RESULTS: TNF-α inhibits the proliferation and tenogenic/osteogenic differentiation of TDSC but, after simultaneous or sequential treatment with TGF-β1 and TNF-α, the expression of tenogenic/osteogenic-related marker and proliferation of TDSC was significantly increased...
February 2, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28152139/bone-morphogenetic-protein-7-suppresses-tgf%C3%AE-2-induced-epithelial-mesenchymal-transition-in-the-lens-implications-for-cataract-prevention
#12
Daisy Y Shu, Magdalena C Wojciechowski, Frank J Lovicu
Purpose: Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a key pathologic mechanism underlying cataract. Two members of the transforming growth factor-β (TGFβ) superfamily, TGFβ and bone morphogenetic protein-7 (BMP-7) have functionally distinct roles in EMT. While TGFβ is a potent inducer of EMT, BMP-7 counteracts the fibrogenic activity of TGFβ. We examine the modulating effect of BMP-7 on TGFβ-induced EMT in LECs. Methods: Rat lens epithelial explants were treated exogenously with TGFβ2 alone or in combination with BMP-7 for up to 5 days...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28134270/signal-mingle-micropatterns-of-bmp-2-and-fibronectin-on-soft-biopolymeric-films-regulate-myoblast-shape-and-smad-signaling
#13
Vincent Fitzpatrick, Laure Fourel, Olivier Destaing, Flora Gilde, Corinne Albigès-Rizo, Catherine Picart, Thomas Boudou
In vivo, bone morphogenetic protein 2 (BMP-2) exists both in solution and bound to the extracellular matrix (ECM). While these two modes of presentation are known to influence cell behavior distinctly, their role in the niche microenvironment and their functional relevance in the genesis of a biological response has sparsely been investigated at a cellular level. Here we used the natural affinity of BMP-2 for fibronectin (FN) to engineer cell-sized micropatterns of BMP-2. This technique allowed the simultaneous control of the spatial presentation of fibronectin-bound BMP-2 and cell spreading...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28128304/targeting-osteoblastic-casein-kinase-2-interacting-protein-1-to-enhance-smad-dependent-bmp-signaling-and-reverse-bone-formation-reduction-in-glucocorticoid-induced-osteoporosis
#14
Jin Liu, Changwei Lu, Xiaohao Wu, Zongkang Zhang, Jie Li, Baosheng Guo, Defang Li, Chao Liang, Lei Dang, Xiaohua Pan, Songlin Peng, Aiping Lu, Baoting Zhang, Ge Zhang
The underlying mechanism of the reduced bone formation during the development of glucocorticoid-induced osteoporosis (GIO) remains unclear. Here, we found that the highly expressed CKIP-1 together with lowly expressed total and phosphorylated Smad1/5 in bone samples was accompanied by either the reduced serum bone formation markers in GIO patients or the decreased bone formation in GIO mice. In vitro studies showed that the highly expressed CKIP-1 could promote Smad1 ubiquitination to suppress the Smad-dependent BMP signaling and inhibit osteogenic differentiation and mineral deposition in MC3T3-E1 cells during glucocorticoid treatment...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28126904/biochemical-and-cellular-analysis-reveals-ligand-binding-specificities-a-molecular-basis-for-ligand-recognition-and-membrane-association-dependent-activities-of-cripto-1-and-cryptic
#15
Senem Aykul, Anthony Parenti, Kit Yee Chu, Jake Reske, Monique Floer, Amy Ralston, Erik Martinez-Hackert
Transforming growth factor β (TGF-β) pathways are key determinants of cell fate in animals. Their basic mechanism of action is simple. However, to produce cell-specific responses, TGF-β pathways are heavily regulated by secondary factors, such as membrane-associated EGF-CFC family proteins. Cellular activities of EGF-CFC proteins have been described, but their molecular functions, including how the mammalian homologs Cripto-1 and Cryptic recognize and regulate TGF-β family ligands, are less clear. Here we use purified human Cripto-1 and mouse Cryptic produced in mammalian cells to show that these two EGF-CFC homologs have distinct, highly specific ligand binding activities...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28124060/bone-morphogenetic-protein-4-regulates-micrornas-mir-494-and-mir-126-5p-in-control-of-endothelial-cell-function-in-angiogenesis
#16
Jennifer S Esser, Erika Saretzki, Franziska Pankratz, Bianca Engert, Sebastian Grundmann, Christoph Bode, Martin Moser, Qian Zhou
MicroRNAs are small non-coding RNAs that negatively regulate posttranscriptional gene expression. Several microRNAs have been described to regulate the process of angiogenesis. Previously, we have shown that bone morphogenetic protein 4 (BMP4) increased the pro-angiogenic activity of endothelial cells. In this project, we now investigated how the pro-angiogenic BMP4 effect is mediated by microRNAs. First, we performed a microRNA array with BMP4-stimulated human umbilical vein endothelial cells (HUVECs). Among the top-regulated microRNAs, we detected a decreased expression of miR-494 and increased expression of miR-126-5p...
January 26, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28059064/bmp-restricts-stemness-of-intestinal-lgr5-stem-cells-by-directly-suppressing-their-signature-genes
#17
Zhen Qi, Yehua Li, Bing Zhao, Chi Xu, Yuan Liu, Haonan Li, Bingjie Zhang, Xinquan Wang, Xiao Yang, Wei Xie, Baojie Li, Jing-Dong Jackie Han, Ye-Guang Chen
The intestinal epithelium possesses a remarkable self-renewal ability, which is mediated by actively proliferating Lgr5(+) stem cells. Bone morphogenetic protein (BMP) signalling represents one major counterforce that limits the hyperproliferation of intestinal epithelium, but the exact mechanism remains elusive. Here we demonstrate that epithelial BMP signalling plays an indispensable role in restricting Lgr5(+) stem cell expansion to maintain intestinal homeostasis and prevent premalignant hyperproliferation on damage...
January 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28040510/du-huo-ji-sheng-tang-and-its-active-component-ligusticum-chuanxiong-promote-osteogenic-differentiation-and-decrease-the-aging-process-of-human-mesenchymal-stem-cells
#18
Jir-You Wang, Che-Sheng Wen, Shih-Chieh Hung, Pei-Wen Chen, Jen-Hwey Chiu
ETHNOPHARMACOLOGICAL RELEVANCE: Postmenopausal osteoporosis is the most common bone disease worldwide. Information concerning the effects of herbal medicines on mesenchymal cell osteogenesis and senescence remains lacking. AIM OF THIS STUDY: This study was designed to investigate the effects of Du-Huo-Ji-Sheng-Tang (DHJST), a Chinese herbal medicine and its active component Ligusticum chuanxiong on osteogenic differentiation and the aging process of human mesenchymal cells (hMSCs)...
December 28, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28030800/the-role-of-mir-17-92-in-the-miregulatory-landscape-of-ewing-sarcoma
#19
Raphaela Schwentner, David Herrero-Martin, Maximilian O Kauer, Cornelia N Mutz, Anna M Katschnig, Grzegorz Sienski, Javier Alonso, Dave Nt Aryee, Heinrich Kovar
MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3'UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing sarcoma. MiR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be among the top EWS-FLI1 activated miRNAs...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029182/nedd4-deficiency-in-vascular-smooth-muscle-promotes-vascular-calcification-by-stabilizing-psmad1
#20
Ji-Hyun Lee, Seon-Ae Jeon, Byung-Gyu Kim, Michiko Takeda, Jae-Jin Cho, Dong-Ik Kim, Hiroshi Kawabe, Je-Yoel Cho
The nonosseous calcification process such as atherosclerosis is one of the major complications in several types of metabolic diseases. In previous study, we uncovered that aberrant activity of TGF-β signaling pathway could contribute the vascular smooth muscle cells (VSMCs) calcification process. Also, we identified NEDD4 E3 ligase as a key suppressor of BMP/Smad pathway via a polyubiquitination dependent selective degradation of C-terminal phosphorylated Smad1 (pSmad1) activated by TGF-β⋅ Here, we further validated and confirmed the role of Nedd4 in in vivo vascular calcification progression...
December 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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