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https://www.readbyqxmd.com/read/28542453/extracellular-calcium-promotes-bone-formation-from-bone-marrow-mesenchymal-stem-cells-by-amplifying-the-effects-of-bmp-2-on-smad-signalling
#1
Rubén Aquino-Martínez, Natalia Artigas, Beatriz Gámez, José Luis Rosa, Francesc Ventura
Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28530121/glucocorticoids-retain-bi-potent-fibroblast-progenitors-during-alveolar-septation-in-mice
#2
Stephen E McGowan, Diann M McCoy
Glucocorticoids have been widely used and exert pleiotropic effects on alveolar structure and function, but do not improve the long-term clinical outcomes for patients with bronchopulmonary dysplasia, emphysema, or interstitial lung diseases. Treatments which foster alveolar regeneration could substantially improve the long-term outcomes for such patients. One approach to alveolar regeneration is to stimulate and guide intrinsic alveolar progenitors along developmental pathways used during secondary septation...
May 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28509082/atg7-mediated-autophagy-is-involved-in-the-neural-crest-cell-generation-in-chick-embryo
#3
Guang Wang, En-Ni Chen, Chang Liang, Jianxin Liang, Lin-Rui Gao, Manli Chuai, Andrea Münsterberg, Yongping Bao, Liu Cao, Xuesong Yang
Autophagy plays a very important role in numerous physiological and pathological events. However, it still remains unclear whether Atg7-induced autophagy is involved in the regulation of neural crest cell production. In this study, we found the co-location of Atg7 and Pax7(+) neural crest cells in early chick embryo development. Upregulation of Atg7 with unilateral transfection of full-length Atg7 increased Pax7(+) and HNK-1(+) cephalic and trunk neural crest cell numbers compared to either Control-GFP transfection or opposite neural tubes, suggesting that Atg7 over-expression in neural tubes could enhance the production of neural crest cells...
May 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28494020/pannexin-3-regulates-proliferation-and-differentiation-of-odontoblasts-via-its-hemichannel-activities
#4
Tsutomu Iwamoto, Takashi Nakamura, Masaki Ishikawa, Keigo Yoshizaki, Asuna Sugimoto, Hiroko Ida-Yonemochi, Hayato Ohshima, Masahiro Saito, Yoshihiko Yamada, Satoshi Fukumoto
Highly coordinated regulation of cell proliferation and differentiation contributes to the formation of functionally shaped and sized teeth; however, the mechanism underlying the switch from cell cycle exit to cell differentiation during odontogenesis is poorly understood. Recently, we identified pannexin 3 (Panx3) as a member of the pannexin gap junction protein family from tooth germs. The expression of Panx3 was predominately localized in preodontoblasts that arise from dental papilla cells and can differentiate into dentin-secreting odontoblasts...
2017: PloS One
https://www.readbyqxmd.com/read/28489883/bmp-7-induces-apoptosis-in-human-germinal-center-b-cells-and-is-influenced-by-tgf-%C3%AE-receptor-type-i-alk5
#5
Lise K Bollum, Kanutte Huse, Morten P Oksvold, Baoyan Bai, Vera I Hilden, Lise Forfang, Sun Ok Yoon, Sébastien Wälchli, Erlend B Smeland, June H Myklebust
Selection and maturation of B cells into plasma cells producing high-affinity antibodies occur in germinal centers (GC). GCs form transiently in secondary lymphoid organs upon antigen challenge, and the GC reaction is a highly regulated process. TGF-β is a potent negative regulator, but the influence of other family members including bone morphogenetic proteins (BMPs) is less known. Studies of human peripheral blood B lymphocytes showed that BMP-6 suppressed plasmablast differentiation, whereas BMP-7 induced apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28469774/effects-of-altered-cxcl12-cxcr4-axis-on-bmp2-smad-runx2-osterix-axis-and-osteogenic-gene-expressions-during-osteogenic-differentiation-of-mscs
#6
Zhanghua Li, Wei Wang, Haijia Xu, Yu Ning, Weijun Fang, Wen Liao, Ji Zou, Yi Yang, Ningsheng Shao
This study investigated the effects of altered CXCL12/CXCR4 axis on the bone morphogenetic protein 2 (BMP-2)/Smad/runt-related transcription factor 2 (Runx2)/Osterix (Osx) signal axis and osteogenic gene expression during osteogenic differentiation of mesenchymal stem cells (MSCs), to gain understanding of the link between migration and osteogenic differentiation signal axis and MSCs osteogenic differentiation mechanisms. The pHBAd-MCMV- CXCL12-GFP vector (Ad-CXCL12) was constructed and quantitative polymerase chain reaction (qPCR)/western blotting used to determine CXCL12 expression in Ad-CXCL12-transfected MSCs...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28468941/aberrant-caveolin-1-mediated-smad-signaling-and-proliferation-identified-by-analysis-of-adenine-474-deletion-mutation-c-474dela-in-patient-fibroblasts-a-new-perspective-on-the-mechanism-of-pulmonary-hypertension
#7
Glenn Marsboom, Zhenlong Chen, Yang Yuan, Yanmin Zhang, Chinnaswamy Tiruppathi, James E Loyd, Eric D Austin, Roberto F Machado, Richard D Minshall, Jalees Rehman, Asrar B Malik
A heterozygous caveolin-1 c.474delA mutation has been identified in a family with heritable pulmonary arterial hypertension (PAH). This frameshift mutation leads to a caveolin-1 protein that contains all known functional domains but has a change in only the final 20 amino acids of the C-terminus. Here we studied how this mutation alters caveolin-1 function, using patient-derived fibroblasts. Transmission electron microscopy showed that fibroblasts carrying the c.474delA mutation form typical caveolae. Expression of mutated caveolin-1 in caveolin-1-null mouse fibroblasts failed to induce formation of caveolae due to retention of the mutated protein in the endoplasmic reticulum...
May 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28467498/spatial-regulation-of-bone-morphogenetic-proteins-bmps-in-postnatal-articular-and-growth-plate-cartilage
#8
Presley Garrison, Shanna Yue, Jeffrey Hanson, Jeffrey Baron, Julian C Lui
Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers-the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28465413/bmp8a-sustains-spermatogenesis-by-activating-both-smad1-5-8-and-smad2-3-in-spermatogonia
#9
Fang-Ju Wu, Ting-Yu Lin, Li-Ying Sung, Wei-Fang Chang, Po-Chih Wu, Ching-Wei Luo
Mutation in either of the genes encoding bone morphogenetic protein (BMP) 8A or 8B (Bmp8a or Bmp8b) causes postnatal depletion of spermatogonia in mice. We found that Bmp8a, but not Bmp8b, was expressed predominantly in the neonatal mouse spermatogonia. Although most BMPs induce activation of SMADs 1, 5, and 8 (SMAD1/5/8), but not SMADs 2 and 3 (SMAD2/3), we found that BMP8A induced signaling through both sets of transcription factors. In undifferentiated mouse spermatogonia, BMP8A activated SMAD1/5/8 through receptor complexes formed by ALK3 and either ACVR2A or BMPR2 and activated SMAD2/3 through receptor complexes formed by ALK5 and ACVR2A, ACVR2B, or TGFBR2...
May 2, 2017: Science Signaling
https://www.readbyqxmd.com/read/28459464/bone-morphogenetic-protein-signaling-mediated-by-alk-2-and-dlx2-regulates-apoptosis-in-glioma-initiating-cells
#10
E Raja, A Komuro, R Tanabe, S Sakai, Y Ino, N Saito, T Todo, M Morikawa, H Aburatani, D Koinuma, C Iwata, K Miyazono
Bone morphogenetic protein (BMP) signaling exerts antitumor activities in glioblastoma; however, its precise mechanisms remain to be elucidated. Here, we demonstrated that the BMP type I receptor ALK-2 (encoded by the ACVR1 gene) has crucial roles in apoptosis induction of patient-derived glioma-initiating cells (GICs), TGS-01 and TGS-04. We also characterized a BMP target gene, Distal-less homeobox 2 (DLX2), and found that DLX2 promoted apoptosis and neural differentiation of GICs. The tumor-suppressive effects of ALK-2 and DLX2 were further confirmed in a mouse orthotopic transplantation model...
May 1, 2017: Oncogene
https://www.readbyqxmd.com/read/28457943/actin-cytoskeleton-mediates-bmp2-smad-signaling-via-calponin-1-in-preosteoblast-under-simulated-microgravity
#11
Hongjie Xu, Feng Wu, Hongyu Zhang, Chao Yang, Kai Li, Hailong Wang, Honghui Yang, Yue Liu, Bai Ding, Yingjun Tan, Ming Yuan, Yinghui Li, Zhongquan Dai
Microgravity influences the activity of osteoblast, induces actin microfilament disruption and leads to bone loss during spaceflight. Mechanical stress such as gravity, regulates cell function, response and differentiation through dynamic cytoskeleton changes, but the mechanotransduction mechanism remains to be fully elucidated. Previous, we demonstrated actin microfilament mediated osteoblast Cbfa1 responsiveness to BMP2 under simulated microgravity (SMG). Here, we explored a potential molecular and its detailed mechanism of actin cytoskeleton functioning on BMP2-Smad signaling in MC3T3-E1 under SMG...
April 27, 2017: Biochimie
https://www.readbyqxmd.com/read/28438754/smad1-5-is-required-for-erythropoietin-mediated-suppression-of-hepcidin-in-mice
#12
Chia-Yu Wang, Amanda B Core, Susanna Canali, Kimberly B Zumbrennen-Bullough, Sinan Ozer, Lieve Umans, An Zwijsen, Jodie L Babitt
Anemia suppresses liver hepcidin expression to supply adequate iron for erythropoiesis. Erythroferrone mediates hepcidin suppression by anemia, but its mechanism of action remains uncertain. The bone morphogenetic protein (BMP)-SMAD signaling pathway has a central role in hepcidin transcriptional regulation. Here, we explored the contribution of individual receptor-activated SMADs in hepcidin regulation and their involvement in erythroferrone suppression of hepcidin. In Hep3B cells, SMAD5 or SMAD1, but not SMAD8, knockdown inhibited hepcidin (HAMP) mRNA expression...
April 24, 2017: Blood
https://www.readbyqxmd.com/read/28427181/metformin-inhibits-alk1-mediated-angiogenesis-via-activation-of-ampk
#13
Ying Ying, Takashi Ueta, Shanshan Jiang, Hui Lin, Yuanyuan Wang, Demetrios Vavvas, Rong Wen, Ye-Guang Chen, Zhijun Luo
Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28397746/non-anticoagulant-heparins-are-hepcidin-antagonists-for-the-treatment-of-anemia
#14
REVIEW
Maura Poli, Michela Asperti, Paola Ruzzenenti, Annamaria Naggi, Paolo Arosio
The peptide hormone hepcidin is a key controller of systemic iron homeostasis, and its expression in the liver is mainly regulated by bone morphogenetic proteins (BMPs), which are heparin binding proteins. In fact, heparins are strong suppressors of hepcidin expression in hepatic cell lines that act by inhibiting the phosphorylation of SMAD1/5/8 proteins elicited by the BMPs. The inhibitory effect of heparins has been demonstrated in cells and in mice, where subcutaneous injections of non-anticoagulant heparins inhibited liver hepcidin expression and increased iron bioavailability...
April 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28389444/bone-morphogenetic-protein-based-therapeutic-approaches
#15
Jonathan W Lowery, Vicki Rosen
Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor (TGF)-β family of ligands and exert most of their effects through the canonical effectors Smad1, 5, and 8. Appropriate regulation of BMP signaling is critical for the development and homeostasis of numerous human organ systems. Aberrations in BMP pathways or their regulation are increasingly associated with diverse human pathologies, and there is an urgent and growing need to develop effective approaches to modulate BMP signaling in the clinic...
April 7, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28377490/biological-role-and-therapeutic-targeting-of-tgf-%C3%AE-3-in-glioblastoma
#16
Katharina Seystahl, Alexandros Papachristodoulou, Isabel Burghardt, Hannah Schneider, Kathy Hasenbach, Michel Janicot, Patrick Roth, Michael Weller
Transforming growth factor (TGF)-β contributes to the malignant phenotype of glioblastoma by promoting invasiveness and angiogenesis and creating an immunosuppressive microenvironment. So far, TGF-β1 and TGF-β2 isoforms have been considered to act in a similar fashion without isoform-specific function in glioblastoma. A pathogenic role for TGF-β3 in glioblastoma has not been defined yet. Here we studied the expression and functional role of endogenous and exogenous TGF-β3 in glioblastoma models. TGF-β3 mRNA is expressed in human and murine long-term glioma cell lines as well as in human glioma-initiating cell cultures with expression levels lower than TGF-β1 or TGF-β2 in most cell lines...
April 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28357470/differential-molecular-regulation-of-processing-and-membrane-expression-of-type-i-bmp-receptors-implications-for-signaling
#17
Tal Hirschhorn, Michal Levi-Hofman, Oded Danziger, Nechama I Smorodinsky, Marcelo Ehrlich
The Type-I bone morphogenetic protein receptors (BMPRs), BMPR1A and BMPR1B, present the highest sequence homology among BMPRs, suggestive of functional similitude. However, sequence elements within their extracellular domain, such as signal sequence or N-glycosylation motifs, may result in differential regulation of biosynthetic processing and trafficking and in alterations to receptor function. We show that (i) BMPR1A and the ubiquitous isoform of BMPR1B differed in mode of translocation into the endoplasmic reticulum; and (ii) BMPR1A was N-glycosylated while BMPR1B was not, resulting in greater efficiency of processing and plasma membrane expression of BMPR1A...
March 29, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28352232/dickkopf-3-upregulates-vegf-in-cultured-human-endothelial-cells-by-activating-activin-receptor-like-kinase-1-alk1-pathway
#18
Carla L Busceti, Simona Marchitti, Franca Bianchi, Paola Di Pietro, Barbara Riozzi, Rosita Stanzione, Milena Cannella, Giuseppe Battaglia, Valeria Bruno, Massimo Volpe, Francesco Fornai, Ferdinando Nicoletti, Speranza Rubattu
Dkk-3 is a member of the dickkopf protein family of secreted inhibitors of the Wnt pathway, which has been shown to enhance angiogenesis. The mechanism underlying this effect is currently unknown. Here, we used cultured HUVECs to study the involvement of the TGF-β and VEGF on the angiogenic effect of Dkk-3. Addition of hrDkk-3 peptide (1 or 10 ng/ml) to HUVECs for 6 or 12 h enhanced the intracellular and extracellular VEGF protein levels, as assessed by RTPCR, immunoblotting, immunocytochemistry and ELISA...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28351832/gonad-related-factors-promote-muscle-performance-gain-during-postnatal-development-in-male-and-female-mice
#19
Vanessa Ueberschlag-Pitiot, Amalia Stantzou, Julien Messéant, Megane Lemaitre, Daniel J Owens, Philippe Noirez, Pauline Roy, Onnik Agbulut, Daniel Metzger, Arnaud Ferry
In order to better define the role of male and female gonad-related factors (MGRF, presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb skeletal muscle contractile performance/function gain during postnatal development, we analysed the effect of castration initiated before puberty in male and female mice. We found that muscle absolute and specific (normalized to muscle weight) maximal forces were decreased in 6-month old male and female castrated mice, as compared to age- and sex-matched intact mice, without alteration in neuromuscular transmission...
March 28, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28327634/scleraxis-is-required-for-maturation-of-tissue-domains-for-proper-integration-of-the-musculoskeletal-system
#20
Yuki Yoshimoto, Aki Takimoto, Hitomi Watanabe, Yuji Hiraki, Gen Kondoh, Chisa Shukunami
Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is expressed persistently in tendons/ligaments, but transiently in entheseal cartilage. In this study, we generated a novel Scx(Cre) knock-in (KI) allele, by in-frame replacement of most of Scx exon 1 with Cre recombinase (Cre), to drive Cre expression using Scx promoter and to inactivate the endogenous Scx. Reflecting the intensity and duration of endogenous expression, Cre-mediated excision occurs in tendinous and ligamentous tissues persistently expressing Scx...
March 22, 2017: Scientific Reports
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