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BMP AND smad

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https://www.readbyqxmd.com/read/28725489/bmp-2-induces-emt-and-breast-cancer-stemness-through-rb-and-cd44
#1
Peide Huang, Anan Chen, Weiyi He, Zhen Li, Guanglin Zhang, Zhong Liu, Ge Liu, Xueting Liu, Shuilian He, Gang Xiao, Feicheng Huang, Jan Stenvang, Nils Brünner, An Hong, Ju Wang
Bone morphogenetic protein 2 (BMP-2) has been reported to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer xenograft models. To investigate the role of BMP-2 in the development of breast cancer stem cells (BCSCs), and to further elucidate the mechanisms underlying its influence on breast cancer metastasis, we conducted a comprehensive molecular study using breast cancer cell lines and clinical samples. Our results showed that downregulation of Rb by BMP-2 was associated with ubiquitin-mediated degradation activated by phosphorylation of Rb via the PI3K/AKT signal pathway...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28718708/enhanced-bone-repair-induced-by-human-adipose-derived-stem-cells-on-osteogenic-extracellular-matrix-ornamented-small-intestinal-submucosa
#2
Chi Zhang, Mei Li, Jinjin Zhu, Fangmiao Luo, Jiyuan Zhao
AIM: Our aim was to design an osteogenic extracellular matrix (ECM) coated bioscaffold and to apply it to critical bone defect repair with adipose-derived stem cells (ADSCs). MATERIALS & METHODS: Morphology of scaffolds was scanned by scanning electron microscope. Cell adhesion, proliferation and osteogenic differentiation of ADSCs on ECM-small intestinal submucosa (SIS) were evaluated by immunofluorescences staining, cell counting kit-8 and real-time qPCR, respectively...
July 18, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28704388/the-mir-23a-27a-24-2-microrna-cluster-buffers-transcription-and-signaling-pathways-during-hematopoiesis
#3
Jeffrey L Kurkewich, Justin Hansen, Nathan Klopfenstein, Helen Zhang, Christian Wood, Austin Boucher, Joseph Hickman, David E Muench, H Leighton Grimes, Richard Dahl
MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models. This polarization is observed early in hematopoietic development, with an increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid progenitor subsets in adult bone marrow. The pool size of multipotential progenitors (MPPs) is unchanged; however, in this report we observe by flow cytometry that polarized subsets of MPPs are changed in the absence of mirn23a...
July 13, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28703293/bmp-and-tgf%C3%AE-signaling-regulate-the-formation-of-m%C3%A3-ller-glia-derived-progenitor-cells-in-the-avian-retina
#4
Levi Todd, Isabella Palazzo, Natalie Squires, Ninoshka Mendonca, Andy J Fischer
Müller glia-derived progenitor cells (MGPCs) have the capability to regenerate neurons in the retinas of different vertebrate orders. The formation of MGPCs is regulated by a network of cell-signaling pathways. The purpose of this study was to investigate how BMP/Smad1/5/8- and TGFβ/Smad2/3-signaling are coordinated to influence the formation of MGPCs in the chick model system. We find that pSmad1/5/8 is selectively up-regulated in the nuclei of Müller glia following treatment with BMP4, FGF2, or NMDA-induced damage, and this up-regulation is blocked by a dorsomorphin analogue DMH1...
July 13, 2017: Glia
https://www.readbyqxmd.com/read/28697500/cx43-and-smad-mediated-tgf-%C3%AE-bmp-signaling-pathway-promotes-cartilage-differentiation-of-bone-marrow-mesenchymal-stem-cells-and-inhibits-osteoblast-differentiation
#5
Ya-Dong Zhang, Shi-Chang Zhao, Zhong-Sheng Zhu, Yi-Fei Wang, Jian-Xiang Liu, Zhi-Cai Zhang, Feng Xue
BACKGROUND/AIMS: The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-β/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. METHODS: BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes...
July 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28688217/yes-associated-protein-1-promotes-the-differentiation-and-mineralization-of-cementoblast
#6
Beining Yang, Hualing Sun, Fangfang Song, Yanru Wu, Jiawei Wang
Yes-associated protein 1 (YAP1) transcriptional coactivator is a mediator of mechanosensitive signaling. Cementum, which covers the tooth root surface, continuously senses external mechanical stimulation. Cementoblasts are responsible for the mineralization and maturation of the cementum. However, the effect of YAP1 on cementoblast differentiation remains largely unknown. In this study, we initially demonstrated that YAP1 overexpression enhanced the mineralization ability of cementoblasts. YAP1 upregulated the mRNA and protein expression of several cementogenesis markers, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and dentin matrix acidic phosphoprotein 1 (DMP1)...
July 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28684382/a-regulatory-role-of-androgen-in-ovarian-steroidogenesis-by-rat-granulosa-cells
#7
Toru Hasegawa, Yasuhiko Kamada, Takeshi Hosoya, Shiho Fujita, Yuki Nishiyama, Nahoko Iwata, Yuji Hiramatsu, Fumio Otsuka
Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells...
July 3, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28680581/endothelial-follistatin-like-1-regulates-the-postnatal-development-of-the-pulmonary-vasculature-by-modulating-bmp-smad-signaling
#8
Navessa P Tania, Harm Maarsingh, I Sophie T Bos, Andrea Mattiotti, Stuti Prakash, Wim Timens, Quinn D Gunst, Luis J Jimenez-Borreguero, Martina Schmidt, Maurice J B van den Hoff, Reinoud Gosens
Bone morphogenetic protein (BMP) signaling regulates vascular smooth muscle maturation, endothelial cell proliferation, and tube formation. The endogenous BMP antagonist Follistatin-like 1 (Fstl1) is highly expressed in pulmonary vascular endothelium of the developing mouse lung, suggesting a role in pulmonary vascular formation and vascular homeostasis. The aim of this study was to investigate the role of Fstl1 in the pulmonary vascular endothelium. To this aim, Fstl1 was conditionally deleted from endothelial and endothelial-derived cells using Tie2-cre driven Fstl1-KO mice (Fstl1-eKO mice)...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28680159/peptides-derived-from-the-knuckle-epitope-of-bmp-9-induce-the-cholinergic-differentiation-and-inactivate-gsk3beta-in-human-sh-sy5y-neuroblastoma-cells
#9
Marc-Antoine Lauzon, Olivier Drevelle, Nathalie Faucheux
The incidence of brain degenerative disorders like Alzheimer's disease (AD) will increase as the world population ages. While there is presently no known cure for AD and current treatments having only a transient effect, an increasing number of publications indicate that growth factors (GF) may be used to treat AD. GFs like the bone morphogenetic proteins (BMPs), especially BMP-9, affect many aspects of AD. However, BMP-9 is a big protein that cannot readily cross the blood-brain barrier. We have therefore studied the effects of two small peptides derived from BMP-9 (pBMP-9 and SpBMP-9)...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28656211/notch-signaling-pathway-promotes-osteogenic-differentiation-of-mesenchymal-stem-cells-by-enhancing-bmp9-smad-signaling
#10
Junjie Cao, Yalin Wei, Jing Lian, Lunyun Yang, Xiaoyan Zhang, Jiaying Xie, Qiang Liu, Jinyong Luo, Baicheng He, Min Tang
Notch is an important pathway in that it regulates cell-to-cell signal transduction, which plays an essential role in skeletal remodeling. Bone morphogenetic protein (BMP)9 has been regarded as one of the most efficient BMPs by which to induce osteogenic differentiation in mesenchymal stem cells (MSCs). Understanding the interaction between Notch and BMP9 signaling is a critical issue for optimizing the application of MSCs and BMPs in bone tissue engineering. In the present study, we investigated the role of Notch signaling in the BMP9‑induced osteogenic differentiation of MSCs...
June 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28646109/bone-morphogenetic-protein-bmp-9-and-bmp10-enhance-tumor-necrosis-factor-%C3%AE-induced-monocyte-recruitment-to-the-vascular-endothelium-mainly-via-activin-receptor-like-kinase-2
#11
Claudia-Gabriela Mitrofan, Sarah L Appleby, Gerard B Nash, Ziad Mallat, Edwin R Chilvers, Paul D Upton, Nicholas W Morrell
Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyte-endothelial interactions using an in vitro flow adhesion assay. Herein, we report that while BMP9/BMP10 alone had no effect on monocyte recruitment, at higher concentrations both cytokines synergised with Tumor necrosis factor-α (TNFα) to increase recruitment to the vascular endothelium. The BMP9/BMP10-mediated increase in monocyte recruitment in the presence of TNFα was associated with upregulated expression levels of E-selectin, VCAM-1 and ICAM-1 on endothelial cells...
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28642261/transforming-growth-factor-beta-stimulates-smad1-5-signaling-in-pulmonary-artery-smooth-muscle-cells-and-fibroblasts-of-the-newborn-mouse-through-alk1
#12
Huili Zhang, Lili Du, Ying Zhong, Kathleen C Flanders, Jesse D Roberts
The intracellular signaling mechanisms through which TGFβ regulates pulmonary development are incompletely understood. Canonical TGFβ signaling involves Smad2/3 phosphorylation, Smad2/3·Smad4 complex formation and nuclear localization, and gene regulation. Here we show that physiologically relevant TGFβ1 levels also stimulate Smad1/5 phosphorylation, typically a mediator of bone morphogenetic protein (BMP) signaling, in mouse pup pulmonary artery smooth muscle cells (mPASMC) and lung fibroblasts and other interstitial lung cell lines...
June 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28641928/bmpr1a-is-a-major-type-1-bmp-receptor-for-bmp-smad-signaling-during-skull-development
#13
Haichun Pan, Honghao Zhang, Ponnu Abraham, Yoshihiro Komatsu, Karen Lyons, Vesa Kaartinen, Yuji Mishina
Craniosynostosis is caused by premature fusion of one or more sutures in an infant skull, resulting in abnormal facial features. The molecular and cellular mechanisms by which genetic mutations cause craniosynostosis are incompletely characterized, and many of the causative genes for diverse types of syndromic craniosynostosis have not yet been identified. We previously demonstrated that augmentation of BMP signaling mediated by a constitutively active BMP type IA receptor (ca-BmpR1A) in neural crest cells (ca1A hereafter) causes craniosynostosis and superimposition of heterozygous null mutation of Bmpr1a rescues premature suture fusion (ca1A;1aH hereafter)...
June 19, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28641655/-il-1%C3%AE-treated-bone-marrow-mesenchymal-stem-cells-enhances-osteogenetic-potential-via-nf-%C3%AE%C2%BAb-pathway
#14
Wei Ye, Xiao-Ming Fei, Yu Tang, Xin-Xin Xu, Yan Zhu
Obsjective:To investigate the effects of differentaction time of IL-1β on the osteogenic capacity of bone marrow mensenchymal cells(BMMSC) and the role of nuclear factor-κB (NF-kB) pathway. METHODS: BMMSC isolated from normal donors was treated with IL-1β for 1 or 7 days, respectively. Alkaline phosphatase (ALP) and alizarin red(AR) stainings were used to detect the osteogenic differentiation potential of BMMSC. The mRNA expression of EphB4, IGF-1 and OPG in BMMSC was measured by real-time PCR...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28627372/regulatory-role-of-melatonin-and-bmp-4-in-prolactin-production-by-rat-pituitary-lactotrope-gh3-cells
#15
Kanako Ogura-Ochi, Satoshi Fujisawa, Nahoko Iwata, Motoshi Komatsubara, Yuki Nishiyama, Naoko Tsukamoto-Yamauchi, Kenichi Inagaki, Jun Wada, Fumio Otsuka
The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT2 receptor was predominantly expressed in GH3 cells, and the inhibitory effects of melatonin on prolactin production were reversed by treatment with the receptor antagonist luzindole, suggesting functional involvement of MT2 action in the suppression of prolactin release...
June 13, 2017: Peptides
https://www.readbyqxmd.com/read/28602823/structural-basis-for-specific-interaction-of-tgf%C3%AE-signaling-regulators-sara-endofin-with-hd-ptp
#16
Deepankar Gahloth, Colin Levy, Louise Walker, Lydia Wunderley, A Paul Mould, Sandra Taylor, Philip Woodman, Lydia Tabernero
SARA and endofin are endosomal adaptor proteins that drive Smad phosphorylation by ligand-activated transforming growth factor β/bone morphogenetic protein (TGFβ/BMP) receptors. We show in this study that SARA and endofin also recruit the tumor supressor HD-PTP, a master regulator of endosomal sorting and ESCRT-dependent receptor downregulation. High-affinity interactions occur between the SARA/endofin N termini, and the conserved hydrophobic region in the HD-PTP Bro1 domain that binds CHMP4/ESCRT-III. CHMP4 engagement is a universal feature of Bro1 proteins, but SARA/endofin binding is specific to HD-PTP...
July 5, 2017: Structure
https://www.readbyqxmd.com/read/28595186/age-related-insulin-like-growth-factor-binding-protein-4-overexpression-inhibits-osteogenic-differentiation-of-rat-mesenchymal-stem-cells
#17
Jinhui Wu, Chao Wang, Xiong Miao, Yungang Wu, Jiabin Yuan, Muchen Ding, Jingfeng Li, Zhicai Shi
BACKGROUND/AIMS: Insulin-like growth factor binding proteins (IGFBP) play important roles in bone metabolism. IGFBP4 is involved in senescent-associated phenomena in mesenchymal stem cells (MSCs). The goal of the present study was to determine whether age-related IGFBP4 overexpression is associated with the impaired osteogenic differentiation potential of aged bone marrow derived MSCs. METHODS: MSCs were isolated from Sprague-Dawley rats aged 3-26 months. The bone morphogenetic protein (BMP)-2-induced osteogenic differentiation of rat MSCs was assessed by analyzing the expression levels of osteoblast marker genes [runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteocalcin (OC)], ALP activity and calcification...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28585096/cellular-citrate-levels-establish-a-regulatory-link-between-energy-metabolism-and-the-hepatic-iron-hormone-hepcidin
#18
Ana Rita da Silva, Joana Neves, Katarzyna Mleczko-Sanecka, Amol Tandon, Sven W Sauer, Matthias W Hentze, Martina U Muckenthaler
Expression of the hepatic peptide hormone hepcidin responds to iron levels via BMP/SMAD signaling, to inflammatory cues via JAK/STAT signaling, to the nutrient-sensing mTOR pathway, as well as to proliferative signals and gluconeogenesis. Here, we asked the question whether hepcidin expression is altered by metabolites generated by intermediary metabolism. To identify such metabolites, we took advantage of a comprehensive RNAi screen, which revealed effectors involved in citrate metabolism. We show that the inhibition of citrate-consuming enzymes increases hepcidin mRNA expression in primary murine hepatocytes...
August 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28584575/melanin-extract-from-gallus-gallus-domesticus-promotes-proliferation-and-differentiation-of-osteoblastic-mg-63-cells-via-bone-morphogenetic-protein-2-signaling
#19
Han-Seok Yoo, Kang-Hyun Chung, Kwon-Jai Lee, Dong-Hee Kim, Jeung Hee An
BACKGROUND/OBJECTIVES: Gallus gallus domesticus (GD) is a natural mutant breed of chicken in Korea with an atypical characterization of melanin in its tissue. This study investigated the effects of melanin extracts of GD on osteoblast differentiation and inhibition of osteoclast formation. MATERIALS/METHODS: The effects of the melanin extract of GD on human osteoblast MG-63 cell differentiation were examined by evaluating cell viability, osteoblast differentiation, and expression of osteoblast-specific transcription factors such as bone morphogenetic protein 2 (BMP-2), small mothers against decapentaplegic homologs 5 (SMAD5), runt-related transcription factor 2 (RUNX2), osteocalcin and type 1 collagen (COL-1) by reverse transcription-polymerase chain reaction and western blotting analysis...
June 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/28578352/endogenous-parathyroid-hormone-promotes-fracture-healing-by-increasing-expression-of-bmpr2-through-camp-pka-creb-pathway-in-mice
#20
Wei Zhou, Lipeng Yu, Jin Fan, Bowen Wan, Tao Jiang, Jian Yin, Yao Huang, Qingqing Li, Guoyong Yin, Zhaoxing Hu
BACKGROUND/AIMS: Endogenous parathyroid hormone (PTH) plays an important role in fracture healing. This study investigated whether endogenous PTH regulates fracture healing by bone morphogenetic protein (BMP) and/or the transforming growth factor-β (TGF-β) signaling pathway. METHODS: Eight-week-old wild-type (WT) and PTH-knockout (PTH KO) male mice were selected, and models of open right-femoral fracture were constructed. Fracture healing and callus characteristics of mice in the two groups were compared by X-ray, micro-computed tomography, histological, and immunohistochemical examinations...
2017: Cellular Physiology and Biochemistry
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