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https://www.readbyqxmd.com/read/29129645/incretins-modulate-progesterone-biosynthesis-by-regulating-bone-morphogenetic-protein-activity-in-rat-granulosa-cells
#1
Yuki Nishiyama, Toru Hasegawa, Shiho Fujita, Nahoko Iwata, Satoko Nagao, Takeshi Hosoya, Kenichi Inagaki, Jun Wada, Fumio Otsuka
The effects of incretins on ovarian steroidogenesis have not been clarified. In this study, we investigated the effects of incretins, including GIP and GLP-1, on ovarian steroidogenesis using rat primary granulosa cells. Treatment with incretins significantly suppressed progesterone synthesis in the presence of FSH, and the effect of GIP was more potent than that of GLP-1. In contrast, incretins had no significant effect on estrogen synthesis by rat granulosa cells. In accordance with the effects of incretins on steroidogenesis, GIP and GLP-1 suppressed the expression of progesterogenic factors and enzymes, including StAR, P450scc, 3βHSD, but not P450arom, and cellular cAMP synthesis induced by FSH...
November 9, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29113455/hdac1-governs-iron-homeostasis-independent-of-histone-deacetylation-in-iron-overload-murine-models
#2
Xiangju Yin, Qian Wu, Jitender Monga, Enjun Xie, Hao Wang, Shufen Wang, Huizhen Zhang, Zhan-You Wang, Tianhua Zhou, Yunjun Shi, Jack Rogers, Hening Lin, Junxia Min, Fudi Wang
AIMS: Iron overload disorders are common and could lead to significant morbidity and mortality worldwide. Due to limited treatment options, there is a great need to develop novel strategies to remove the excess body iron. To discover potential epigenetic modulator in hepcidin upregulation and subsequently decreasing iron burden, we performed an epigenetic screen. The in vivo effects of the identified compounds were further tested in iron-overload mouse models, including Hfe-/-, Hjv-/- and hepatocyte-specific Smad4 knockout (Smad4fl/fl;Alb-Cre+) mice...
November 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29094227/down-regulation-of-noggin-and-mir-138-coordinately-promote-osteogenesis-of-mesenchymal-stem-cells
#3
Xing-Kun Sun, Jin Zhou, Lei Zhang, Tian Ma, Yu-Han Wang, Yan-Mei Yang, Yan-Ting Tang, Hong Li, Li-Jun Wang
Mesenchymal stem cells (MSCs) can differentiate to osteocytes under suitable conditions. In recent years, micro-nucleotides have been progressively used to modulate gene expression in cells due to the consideration of safety. Our present study aimed to investigate whether co-delivery of Noggin-siRNA and antimiR-138 enhances the osteogenic effect of MSCs. Using a murine MSC line, C3H/10T1/2 cells, the delivery efficiency of Noggin-siRNA and antimiR-138 into MSCs was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR)...
December 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29091893/isoflurane-post-conditioning-down-regulates-expression-of-aquaporin-4-in-rats-with-cerebral-ischemia-reperfusion-injury-and-is-possibly-related-to-bone-morphogenetic-protein-4-smad1-5-8-signaling-pathway
#4
Min Yuan, Mingyue Ge, Jiangwen Yin, Zhigang Dai, Liping Xie, Yan Li, Xuejiao Liu, Li Peng, Guixing Zhang, Junqiang Si, Ketao Ma, Sheng Wang
AIM: Aquaporins (AQPs) are water-channels that play important roles in brain water homeostasis and cerebral edema induced by brain injury. This study aimed to investigate the relationship between AQP4, bone morphogenetic protein 4 (BMP4)/Smad1/5/8 signaling pathway and isoflurane post-conditiong, which has effects on brain edema in rats with cerebral ischemia/reperfusion (I/R) injury. METHODS: Cerebral I/R injury was induced in rats by using the middle cerebral artery occlusion (MCAO) model for 90min, followed by 24h of reperfusion...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29089047/whole-exome-sequencing-in-342-congenital-cardiac-left-sided-lesion-cases-reveals-extensive-genetic-heterogeneity-and-complex-inheritance-patterns
#5
Alexander H Li, Neil A Hanchard, Dieter Furthner, Susan Fernbach, Mahshid Azamian, Annarita Nicosia, Jill Rosenfeld, Donna Muzny, Lisa C A D'Alessandro, Shaine Morris, Shalini Jhangiani, Dhaval R Parekh, Wayne J Franklin, Mark Lewin, Jeffrey A Towbin, Daniel J Penny, Charles D Fraser, James F Martin, Christine Eng, James R Lupski, Richard A Gibbs, Eric Boerwinkle, John W Belmont
BACKGROUND: Left-sided lesions (LSLs) account for an important fraction of severe congenital cardiovascular malformations (CVMs). The genetic contributions to LSLs are complex, and the mutations that cause these malformations span several diverse biological signaling pathways: TGFB, NOTCH, SHH, and more. Here, we use whole exome sequence data generated in 342 LSL cases to identify likely damaging variants in putative candidate CVM genes. METHODS: Using a series of bioinformatics filters, we focused on genes harboring population-rare, putative loss-of-function (LOF), and predicted damaging variants in 1760 CVM candidate genes constructed a priori from the literature and model organism databases...
October 31, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29044189/tgf-%C3%AE-signalling-and-peg10-are-mutually-exclusive-and-inhibitory-in-chondrosarcoma-cells
#6
Naohiro Shinohara, Shingo Maeda, Yuhei Yahiro, Daisuke Sakuma, Kanehiro Matsuyama, Katsuyuki Imamura, Ichiro Kawamura, Takao Setoguchi, Yasuhiro Ishidou, Satoshi Nagano, Setsuro Komiya
Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling in human chondrosarcomas compared with enchondromas by immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1 chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29039519/runx3-plays-an-important-role-in-mediating-the-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells
#7
Yufeng Wang, Qiaoling Feng, Caixia Ji, Xiaohua Liu, Li Li, Jinyong Luo
Although bone morphogenetic protein 9 (BMP9) is highly capable of promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) both in vitro and in vivo, the molecular mechanisms involved remain to be fully elucidated. Runt-related transcription factor (RUNX)3 is an essential regulator of osteoblast/chondrocyte maturation. However, the exact role of RUNX3 in BMP9 osteoinductive activity is unknown. In this study, we sought to investigate the functional role of RUNX3 in the BMP9-induced osteogenic differentiation of MSCs...
September 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29037671/blue-mussel-mytilus-edulis-protein-hydrolysate-promotes-mouse-mesenchymal-stem-cell-differentiation-into-osteoblasts-through-up-regulation-of-bone-morphogenetic-protein
#8
Jun-Ho Hyung, Chang-Bum Ahn, Jae-Young Je
Seafood provides a range of health benefits due to its high-protein level. In this study, the osteogenic effect of blue mussel (Mytilus edulis) protein hydrolysates (BMPH) on osteoblast differentiation were examined using mouse mesenchymal stem cells (MSCs). A preparation we called BMPH<1kDa which showed the highest osteogenic effect in MSCs, was prepared by peptic hydrolysis. BMPH<1kDa treatment stimulated osteoblast differentiation with alkaline phosphatase (ALP) induction, osteocalcin and type I collagen activity as well as calcium deposition...
March 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29027119/mollugin-enhances-the-osteogenic-action-of-bmp-2-via-the-p38-smad-signaling-pathway
#9
Seong-Hee Moon, Ikyon Kim, Seong Hwan Kim
Bone morphogenetic protein 2 (BMP-2) has been used clinically to encourage bone regeneration; although, there can be major side effects with larger doses. Therefore, there is a need to identify new small molecules to potentiate the osteogenic action of BMP-2. In this study, we investigated the effect of mollugin on bone formation in murine bi-potential mesenchymal progenitor C2C12 cells by combination with BMP-2. We found mollugin could enhance the BMP-2-mediated osteoblast differentiation of C2C12 cells. This was accompanied by the induction of other osteogenic BMPs...
October 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28992339/stat3-inhibition-attenuates-the-progressive-phenotypes-of-alport-syndrome-mouse-model
#10
Tsubasa Yokota, Kohei Omachi, Mary Ann Suico, Misato Kamura, Haruka Kojima, Ryosuke Fukuda, Keishi Motomura, Keisuke Teramoto, Shota Kaseda, Jun Kuwazuru, Toru Takeo, Naomi Nakagata, Tsuyoshi Shuto, Hirofumi Kai
Background: Alport syndrome (AS) is a hereditary, progressive nephritis caused by mutation of type IV collagen. Previous studies have shown that activation of signal transducer and activator of transcription 3 (STAT3) exacerbates other renal diseases, but whether STAT3 activation exacerbates AS pathology is still unknown. Here we aim to investigate the involvement of STAT3 in the progression of AS. Method: Phosphorylated STAT3 expression was assessed by immunoblotting analysis of kidneys and glomeruli of an AS mouse model ( Col4a5 G5X mutant)...
August 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28977600/alk2-alk3-bmpr2-acvr2a-mediate-bmp2-induced-downregulation-of-pentraxin-3-expression-in-human-granulosa-lutein-cells
#11
Long Bai, Hsun-Ming Chang, Jung-Chien Cheng, Guiyan Chu, Peter C K Leung, Gongshe Yang
Bone morphogenetic protein 2 (BMP2) belongs to the transforming growth factor-β superfamily and plays a critical role in regulating ovarian follicle function. Currently, the role of BMP2 during cumulus expansion remains to be determined. The aim of this study was to investigate the effect of BMP2 on the regulation of pentraxin 3 (PTX3) expression (the major component of cumulus expansion) and the underlying mechanisms in human granulosa-lutein (hGL) cells. Both primary and immortalized hGL cells were used as research models...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28973643/tacrolimus-rescues-the-signaling-and-gene-expression-signature-of-endothelial-alk1-loss-of-function-and-improves-hht-vascular-pathology
#12
Santiago Ruiz, Pallavi Chandakkar, Haitian Zhao, Julien Papoin, Prodyot K Chatterjee, Erica Christen, Christine N Metz, Lionel Blanc, Fabien Campagne, Philippe Marambaud
Hereditary hemorrhagic telangiectasia (HHT) is a highly debilitating and life-threatening genetic vascular disorder arising from endothelial cell (EC) proliferation and hypervascularization, for which no cure exists. Because HHT is caused by loss-of-function mutations in BMP9-ALK1-Smad1/5/8 signaling, interventions aimed at activating this pathway are of therapeutic value. We interrogated the whole-transcriptome in human umbilical vein ECs (HUVECs) and found that ALK1 signaling inhibition was associated with a specific pro-angiogenic gene expression signature, which included a significant elevation of DLL4 expression...
September 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28970797/biscarbamate-cross-linked-low-molecular-weight-polyethylenimine-for-delivering-anti-chordin-sirna-into-human-mesenchymal-stem-cells-for-improving-bone-regeneration
#13
Chuandong Wang, Weien Yuan, Fei Xiao, Yaokai Gan, Xiaotian Zhao, Zhanjing Zhai, Xiaoying Zhao, Chen Zhao, Penglei Cui, Tuo Jin, Xiaodong Chen, Xiaoling Zhang
Small-interfering RNA (siRNA) provides a rapid solution for drug design and provides new methods to develop customizable medicines. Polyethyleneimine 25 kDa (PEI25kDa) is an effective transfection agent used in siRNA delivery. However, the lack of degradable linkage causes undesirable toxicity, hindering its clinical application. We designed a low-molecular-weight cross-linked polyethylenimine named PEI-Et (Mn:1220, Mw:2895) by using degradable ethylene biscarbamate linkage with lower cytotoxicity and higher knockdown efficiency than PEI25kDa in delivery Chordin siRNA to human bone mesenchymal stem cells (hBMSCs)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28969002/baicalin-attenuates-monocrotaline-induced-pulmonary-hypertension-through-bone-morphogenetic-protein-signaling-pathway
#14
Zhaohua Zhang, Luan Zhang, Chao Sun, Feng Kong, Jue Wang, Qian Xin, Wen Jiang, Kaili Li, Ou Chen, Yun Luan
Baicalin, a flavonoid compound extracted from roots of Scutellaria baicalensis Georgi (huang qin), it has been shown to effectively attenuates pulmonary hypertension (PH), however, the potential mechanism remains unexplored. In this study, we investigated the potential mechanism of baicalin on monocrotaline (MCT)-induced PH in rats. The results showed that baicalin attenuated lung damage in PH rat model through inhibiting the pulmonary arterial smooth muscle cell proliferation and induction of cells apoptosis...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28945007/nonmineralized-and-mineralized-collagen-scaffolds-induce-differential-osteogenic-signaling-pathways-in-human-mesenchymal-stem-cells
#15
Qi Zhou, Xiaoyan Ren, David Bischoff, Daniel W Weisgerber, Dean T Yamaguchi, Timothy A Miller, Brendan A C Harley, Justine C Lee
The instructive capabilities of extracellular matrix components in progenitor cell differentiation have recently generated significant interest in the development of bioinspired materials for regenerative applications. Previously, a correlation was described between the osteogenic capabilities of nanoparticulate mineralized collagen glycosaminoglycan scaffolds (MC-GAG) and an autogenous activation of small mothers against decapentaplegic ( Smad1/5) in the canonical bone morphogenetic protein receptor (BMPR) pathway with a diminished extracellular signal regulated kinase 1/2 (ERK1/2) activation when compared to nonmineralized collagen glycosaminoglycan scaffolds (Col-GAG)...
September 25, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28943430/microrna-21-promotes-osteogenesis-of-bone-marrow-mesenchymal-stem-cells-via-the-smad7-smad1-5-8-runx2-pathway
#16
Xiaoyan Li, Lijia Guo, Yitong Liu, Yingying Su, Yongmei Xie, Juan Du, Jian Zhou, Gang Ding, Hao Wang, Yuxing Bai, Yi Liu
Bone marrow mesenchymal stem cells (BMMSCs) are pluripotent stem cells, and the osteogenic differentiation of BMMSCs has been drawing attention for a long time. Bone formation is regulated by numerous molecular and cellular signaling pathways, and the differentiation of BMMSCs is controlled by a well-defined genetic program. In the present study, we isolated BMMSCs from the bone cavities of wild-type (WT) and microRNA-21 knock-out (miR-21-KO) mice and found that miR-21 was significantly upregulated during the osteogenic differentiation of BMMSCs...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28934877/activin-and-nodal-are-not-suitable-alternatives-to-tgf%C3%AE-for-chondrogenic-differentiation-of-mesenchymal-stem-cells
#17
Laurie M G de Kroon, Esmeralda N Blaney Davidson, Roberto Narcisi, Eric Farrell, Peter M van der Kraan, Gerjo J V M van Osch
Objective Previously, we demonstrated the importance of transforming growth factor-β (TGFβ)-activated SMAD2/3 signaling in chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). However, TGFβ also signals via the SMAD1/5/9 pathway, which is known to induce terminal differentiation of BMSCs. In this study, we investigated whether other SMAD2/3-activating ligands, Activin and Nodal, can induce chondrogenic differentiation of BMSCs without inducing terminal differentiation. Design Activation of SMAD2/3 signaling and chondrogenesis were evaluated in human BMSCs ( N = 3 donors) stimulated with TGFβ, Activin, or Nodal...
October 2017: Cartilage
https://www.readbyqxmd.com/read/28926103/fam20c-regulates-osteoblast-behaviors-and-intracellular-signaling-pathways-in-a-cell-autonomous-manner
#18
Chao Liu, Hua Zhang, Priyam Jani, Xiaofang Wang, Yongbo Lu, Nan Li, Jing Xiao, Chunlin Qin
Recent studies indicate that Family with sequence similarity 20 member C (FAM20C) catalyzes the phosphorylation of secreted proteins, and participates in a variety of biological processes, including cell proliferation, migration, mineralization, and phosphate homeostasis. To explore the local influences of FAM20C on osteoblast, Fam20c-deficient osteoblasts were generated by treating the immortalized Fam20c(f/f) osteoblasts with CMV-Cre-IRES-EGFP lentivirus. Compared with the normal Fam20c(f/f) osteoblasts, the expression of Bone sialoprotein (Bsp), Osteocalcin (Ocn), Fibroblast growth factor 23 (Fgf23), and transcription factors that promote osteoblast maturation were up-regulated in the Fam20c-deficient osteoblasts...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28926099/anti-osteoporosis-activity-of-sanguinarine-in-preosteoblast-mc3t3-e1-cells-and-an-ovariectomized-rat-model
#19
Fuzhan Zhang, Jile Xie, Genlin Wang, Ge Zhang, Huilin Yang
Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti-inflammatory and anti-tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This study further evaluated the effects of Sanguinarine on the differentiation of murine preosteoblast MC3T3-E1 cells and its anti-osteoporosis activity in an ovarietomized rat model. Sanguinarine treatment (0.25, 0.5, 1 and 2 µM) of MC3T3-E1 cells significantly increased alkaline phosphatase (ALP) activity and the phoshporalyation of AMP-activated protein kinase α subunit (AMPKα), but did not affect cell proliferation...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28923783/bmp7-induced-pten-inhibits-akt-and-prevents-renal-fibrosis
#20
Debra F Higgins, Leah M Ewart, Enda Masterson, Sadhbh Tennant, Gleb Grebnev, Marco Prunotto, Sylvia Pomposiello, Karin Conde-Knape, Finian M Martin, Catherine Godson
Bone morphogenetic protein-7 (BMP-7) counteracts pro-fibrotic effects of TGFβ1 in cultured renal cells and protects from fibrosis in acute and chronic renal injury models. Using the unilateral ureteral obstruction (UUO) model of chronic renal fibrosis, we investigated the effect of exogenous-rhBMP-7 on pro-fibrotic signaling pathways mediated by TGFβ1 and hypoxia. Mice undergoing UUO were treated with vehicle or rhBMP-7 (300μg/kg i.p.) every other day for eight days and kidneys analysed for markers of fibrosis and SMAD, MAPK, and PI3K signaling...
September 18, 2017: Biochimica et Biophysica Acta
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