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BMP AND smad

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https://www.readbyqxmd.com/read/29789443/low-intensity-pulsed-ultrasound-stimulation-facilitates-in-vitro-osteogenic-differentiation-of-human-adipose-derived-stem-cells-via-up-regulation-of-heat-shock-protein-hsp-70-hsp90-and-bone-morphogenetic-protein-bmp-signaling-pathway
#1
Zhonglei Zhang, Yalin Ma, Shaowen Guo, Yi He, Gang Bai, Wenjun Zhang
Low-intensity pulsed ultrasound (LIPUS) has positive effects on osteogenic differentiation. However, the effect of LIPUS on osteogenic differentiation of human adipose-derived stem cells (hASCs) is unclear. In the present study, we investigated whether LIPUS could promote the proliferation and osteogenic differentiation of hASCs. hASCs were isolated and osteogenically induced with LIPUS stimulation at 20 and 30 mW cm-2 for 30 min day-1 Cell proliferation and osteogenic differentiation potential of hASCs were respectively analyzed by cell counting kit-8 assay, Alizarin Red S staining, real-time polymerase chain reaction, and Western blotting...
May 29, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29789425/a-heterodimer-formed-by-bone-morphogenetic-protein-9-bmp9-and-bmp10-provides-most-bmp-biological-activity-in-plasma
#2
Emmanuelle Tillet, Marie Ouarné, Agnès Desroches-Castan, Christine Mallet, Mariela Subileau, Robin Didier, Anna Lioutsko, Guillaume Belthier, Jean-Jacques Feige, Sabine Bailly
Bone morphogenetic protein 9 (BMP9) and BMP10 are the two high-affinity ligands for the endothelial receptor activin receptor-like kinase 1 (ALK1) and are key regulators of vascular remodeling. They are both present in the blood, but their respective biological activities are still a matter of debate. The aim of the present work was to characterize their circulating forms to better understand how their activities are regulated in vivo. First, by cotransfecting BMP9 and BMP10, we found that both can form a disulfide-bonded heterodimer in vitro and that this heterodimer is functional on endothelial cells via ALK1...
May 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29784997/mechanics-guided-embryonic-patterning-of-neuroectoderm-tissue-from-human-pluripotent-stem-cells
#3
Xufeng Xue, Yubing Sun, Agnes M Resto-Irizarry, Ye Yuan, Koh Meng Aw Yong, Yi Zheng, Shinuo Weng, Yue Shao, Yimin Chai, Lorenz Studer, Jianping Fu
Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo...
May 21, 2018: Nature Materials
https://www.readbyqxmd.com/read/29780169/mediator-kinase-cdk8-cdk19-drives-yap1-dependent-bmp4-induced-emt-in-cancer
#4
Anne Serrao, Laura M Jenkins, Alexander A Chumanevich, Ben Horst, Jiaxin Liang, Michael L Gatza, Nam Y Lee, Igor B Roninson, Eugenia V Broude, Karthikeyan Mythreye
CDK8 is a transcription-regulating kinase that controls TGF-β/BMP-responsive SMAD transcriptional activation and turnover through YAP1 recruitment. However, how the CDK8/YAP1 pathway influences SMAD1 response in cancer remains unclear. Here we report that SMAD1-driven epithelial-to-mesenchymal transition (EMT) is critically dependent on matrix rigidity and YAP1 in a wide spectrum of cancer models. We find that both genetic and pharmacological inhibition of CDK8 and its homologous twin kinase CDK19 leads to abrogation of BMP-induced EMT...
May 21, 2018: Oncogene
https://www.readbyqxmd.com/read/29752282/niche-mediated-bmp-smad-signaling-regulates-lung-alveolar-stem-cell-proliferation-and-differentiation
#5
Mei-I Chung, Melissa Bujnis, Christina E Barkauskas, Yoshihiko Kobayashi, Brigid L M Hogan
The bone morphogenetic protein (BMP) signaling pathway, including antagonists, functions in lung development and regeneration of tracheal epithelium from basal stem cells. Here, we explore its role in the alveolar region, where type 2 epithelial cells (AT2s) and Pdgfrα+ type 2-associated stromal cells (TASCs) are components of the stem cell niche. We use organoids and in vivo alveolar regrowth after pneumonectomy (PNX) - a process that requires proliferation of AT2s and differentiation into type 1 cells (AT1s)...
May 11, 2018: Development
https://www.readbyqxmd.com/read/29751129/selective-inhibition-of-src-family-kinases-by-su6656-increases-bone-mass-by-uncoupling-bone-formation-from-resorption-in-mice
#6
Cyril Thouverey, Serge Ferrari, Joseph Caverzasio
Mice deficient in the non-receptor tyrosine kinase Src exhibit high bone mass due to impaired bone resorption and increased bone formation. Although several Src family kinase inhibitors inhibit bone resorption in vivo, they display variable effects on bone formation. SU6656 is a selective Src family kinase inhibitor with weaker activity towards the non-receptor tyrosine kinase Abl and receptor tyrosine kinases which are required for appropriate osteoblast proliferation, differentiation and function. Therefore, we sought to determine whether SU6656 could increase bone mass by inhibiting bone resorption and by stimulating bone formation, and to explore its mechanisms of action...
May 8, 2018: Bone
https://www.readbyqxmd.com/read/29743489/magnetic-mesoporous-calcium-sillicate-chitosan-porous-scaffolds-for-enhanced-bone-regeneration-and-photothermal-chemotherapy-of-osteosarcoma
#7
Fan Yang, Jiawei Lu, Qinfei Ke, Xiaoyuan Peng, Yaping Guo, Xuetao Xie
The development of multifunctional biomaterials to repair bone defects after neoplasm removal and inhibit tumor recurrence remained huge clinical challenges. Here, we demonstrate a kind of innovative and multifunctional magnetic mesoporous calcium sillicate/chitosan (MCSC) porous scaffolds, made of M-type ferrite particles (SrFe12 O19 ), mesoporous calcium silicate (CaSiO3 ) and chitosan (CS), which exert robust anti-tumor and bone regeneration properties. The mesopores in the CaSiO3 microspheres contributed to the drug delivery property, and the SrFe12 O19 particles improved photothermal therapy (PTT) conversion efficacy...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29736214/masquelet-s-induced-membrane-promotes-the-osteogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-by-activating-the-smad-and-mapk-pathways
#8
Qian Tang, Minji Tong, Gang Zheng, Liyan Shen, Ping Shang, Haixiao Liu
The Masquelet's induced membrane (IM) technique is widely used to treat large segmental bone defects due to its physical priority and biological function. However, the underlying molecular mechanism of the IM on bone formation remains unknown. In the present study, rat bone marrow-derived mesenchymal stem cells (BMSCs) were used as an in vitro model and bone morphogenetic protein 2 (BMP-2) was used as a positive control to evaluate the effects of the IM on the osteogenic differentiation of BMSCs. Although the IM group did not exhibit a significant increase in the expression of Runt-related transcription factor 2 (Runx2), Collagen I (Col I), osteocalcin (OCN) and alkaline phosphatase (ALP) relative to the BMP-2 administration, the IM was considerably effective compared with the untreated group...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29663368/a-peptide-that-blocks-the-interaction-of-nf-%C3%AE%C2%BAb-p65-subunit-with-smad4-enhances-bmp2-induced-osteogenesis
#9
Mariko Urata, Shoichiro Kokabu, Takuma Matsubara, Goro Sugiyama, Chihiro Nakatomi, Hiroshi Takeuchi, Shizu Hirata-Tsuchiya, Kazuhiro Aoki, Yukihiko Tamura, Yasuko Moriyama, Yasunori Ayukawa, Miho Matsuda, Min Zhang, Kiyoshi Koyano, Chiaki Kitamura, Eijiro Jimi
Bone morphogenetic protein (BMP) potentiates bone formation through the Smad signaling pathway in vitro and in vivo. The transcription factor nuclear factor κB (NF-κB) suppresses BMP-induced osteoblast differentiation. Recently, we identified that the transactivation (TA) 2 domain of p65, a main subunit of NF-κB, interacts with the mad homology (MH) 1 domain of Smad4 to inhibit BMP signaling. Therefore, we further attempted to identify the interacting regions of these two molecules at the amino acid level...
April 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29622677/heparan-sulfate-antagonism-alters-bone-morphogenetic-protein-signaling-and-receptor-dynamics-suggesting-a-mechanism-in-hereditary-multiple-exostoses
#10
Christina Mundy, Evan Yang, Hajime Takano, Paul C Billings, Maurizio Pacifici
Hereditary Multiple Exostoses (HME) is a pediatric disorder caused by heparan sulfate (HS) deficiency and is characterized by growth plate-associated osteochondromas. Previously, we found that osteochondroma formation in mouse models is preceded by ectopic bone morphogenetic protein (BMP) signaling in the perichondrium, but the mechanistic relationships between BMP signaling and HS deficiency remain unclear. Therefore, we used an HS antagonist (Surfen) to investigate the effects of this HS interference on BMP signaling, ligand availability, cell surface BMP receptor (BMPR) dynamics and BMPR interactions in Ad-293 and C3H/10T1/2 cells...
April 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29600572/adenine-alleviates-iron-overload-by-camp-pka-mediated-hepatic-hepcidin-in-mice
#11
Yingqi Zhang, Xudong Wang, Qian Wu, Hao Wang, Lu Zhao, Xinhui Wang, Mingdao Mu, Enjun Xie, Xuyan He, Dandan Shao, Yanna Shang, Yongrong Lai, Yelena Ginzburg, Junxia Min, Fudi Wang
Hemochromatosis is prevalent and often associated with high rates of morbidity and mortality worldwide. The safe alternative iron-reducing approaches are urgently needed in order to better control iron overload. Our unbiased vitamin screen for modulators of hepcidin, a master iron regulatory hormone, identifies adenine (vitamin B4) as a potent hepcidin agonist. Adenine significantly induced hepcidin mRNA level and promoter activity activation in human cell lines, possibly through BMP/SMAD pathway. Further studies in mice validated the effect of adenine on hepcidin upregulation...
March 30, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29587443/the-horizon-of-a-therapy-for-rare-genetic-diseases-a-druggable-future-for-fibrodysplasia-ossificans-progressiva
#12
REVIEW
Serena Cappato, Francesca Giacopelli, Roberto Ravazzolo, Renata Bocciardi
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition characterized by progressive extra-skeletal ossification leading to cumulative and severe disability. FOP has an extremely variable and episodic course and can be induced by trauma, infections, iatrogenic harms, immunization or can occur in an unpredictable way, without any recognizable trigger. The causative gene is ACVR1 , encoding the Alk-2 type I receptor for bone morphogenetic proteins (BMPs). The signaling is initiated by BMP binding to a receptor complex consisting of type I and II molecules and can proceed into the cell through two main pathways, a canonical, SMAD-dependent signaling and a p38-mediated cascade...
March 26, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29577917/msx2-supports-epidermal-competency-during-wound-induced-hair-follicle-neogenesis
#13
Michael W Hughes, Ting-Xin Jiang, Maksim V Plikus, Christian Fernando Guerrero-Juarez, Chein-Hong Lin, Christopher Schafer, Robert Maxson, Randall B Widelitz, Cheng-Ming Chuong
Cutaneous wounds in adult mammals typically heal by scarring. However, large full-thickness wounds undergo wound-induced hair follicle neogenesis (WIHN), a novel form of regeneration. Here, we demonstrate WIHN requires transient expression of epidermal Msx2 in two phases; the wound margin early and the wound center late. Msx2 expression is present in the migrating epithelium during early wound healing, and then presents in the epithelium and mesenchyme later in the wound center. WIHN is abrogated in germline and epithelial-specific Msx2 mutant mice...
March 22, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29575577/smad7-deficiency-decreases-iron-and-haemoglobin-through-hepcidin-up-regulation-by-multilayer-compensatory-mechanisms
#14
Peng An, Hao Wang, Qian Wu, Jiaming Wang, Zhidan Xia, Xuyan He, Xinhui Wang, Yan Chen, Junxia Min, Fudi Wang
To maintain iron homoeostasis, the iron regulatory hormone hepcidin is tightly controlled by BMP-Smad signalling pathway, but the physiological role of Smad7 in hepcidin regulation remains elusive. We generated and characterized hepatocyte-specific Smad7 knockout mice (Smad7Alb/Alb ), which showed decreased serum iron, tissue iron, haemoglobin concentration, up-regulated hepcidin and increased phosphor-Smad1/5/8 levels in both isolated primary hepatocytes and liver tissues. Increased levels of hepcidin lead to reduced expression of intestinal ferroportin and mild iron deficiency anaemia...
March 25, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29571612/kir2-1-is-important-for-efficient-bmp-signaling-in-mammalian-face-development
#15
Matthew T Belus, Madison A Rogers, Alaaeddin Elzubeir, Megan Josey, Steven Rose, Viktoria Andreeva, Pamela C Yelick, Emily A Bates
Mutations that disrupt the inwardly rectifying potassium channel Kir2.1 lead to Andersen-Tawil syndrome that includes periodic paralysis, cardiac arrhythmia, cognitive deficits, craniofacial dysmorphologies and limb defects. The molecular mechanism that underlies the developmental consequences of inhibition of these channels has remained a mystery. We show that while loss of Kir2.1 function does not affect expression of several early facial patterning genes, the domain in which Pou3f3 is expressed in the maxillary arch is reduced...
March 20, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29563538/ucma-grp-inhibits-phosphate-induced-vascular-smooth-muscle-cell-calcification-via-smad-dependent-bmp-signalling
#16
Brecht A Willems, Malgorzata Furmanik, Marjolein M J Caron, Martijn L L Chatrou, Dennis H M Kusters, Tim J M Welting, Michael Stock, Marta S Rafael, Carla S B Viegas, Dina C Simes, Cees Vermeer, Chris P M Reutelingsperger, Leon J Schurgers
Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification...
March 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29552807/-review-for-treatment-effect-and-signaling-pathway-regulation-of-kidney-tonifying-traditional-chinese-medicine-on-osteoporosis
#17
REVIEW
Ya-Ping Xiao, Jie Zeng, Lin-Na Jiao, Xiao-Yu Xu
The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29544628/interaction-of-melatonin-and-bmp-6-in-ovarian-steroidogenesis
#18
Fumio Otsuka
The bone morphogenetic protein (BMP) system in the ovary plays a physiological role as a luteinization inhibitor in growing follicles. BMP-6 secreted from oocytes and granulosa cells can exert an inhibitory effect on follicle-stimulating hormone (FSH) actions by suppressing adenylate cyclase activity downstream of the FSH receptor. The inhibition of FSH-induced progesterone production by BMP-6 is impaired by melatonin treatment in granulosa cells. Intracellular Smad signaling induced by BMP-6 is suppressed by melatonin, suggesting that melatonin has a regulatory role in BMP receptor signaling in granulosa cells...
2018: Vitamins and Hormones
https://www.readbyqxmd.com/read/29544541/highly-efficient-methods-to-obtain-homogeneous-dorsal-neural-progenitor-cells-from-human-and-mouse-embryonic-stem-cells-and-induced-pluripotent-stem-cells
#19
Meixiang Zhang, Justine Ngo, Filomena Pirozzi, Ying-Pu Sun, Anthony Wynshaw-Boris
BACKGROUND: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages...
March 15, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29524422/induction-of-hepatocytes-derived-insulin-producing-cells-using-small-molecules-and-identification-of-microrna-profiles-during-this-procedure
#20
Gui Pan, Haojie Hao, Jianping Liu
The transplantation of insulin-producing cells (IPCs) or pancreatic progenitor cells is a theoretical therapy for diabetes with insulin insufficiency. Isolated hepatocytes from newborn rats (within 24 h after birth) were progressively induced into IPCs using 5-aza-2'-deoxycytidine, Trichostatin A, retinoic acid, insulin-transferrin-selenium, and nicotinamide. We transplanted Pdx1+ pancreatic progenitors into STZ-induced diabetic mice and found the decreased blood glucose and increased insulin level in comparison with diabetic model...
April 6, 2018: Biochemical and Biophysical Research Communications
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