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Bone morphogenetic protein

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https://www.readbyqxmd.com/read/28081379/direct-gingival-fibroblast-osteoblast-transdifferentiation-via-epigenetics
#1
Y Cho, B Kim, H Bae, W Kim, J Baek, K Woo, G Lee, Y Seol, Y Lee, Y Ku, I Rhyu, H Ryoo
Alveolar bone resorption caused by trauma or periodontal diseases has represented a challenge for both dental clinicians and researchers. In this study, we evaluate the osteogenic potential of human gingival fibroblasts (HGFs) through a direct transdifferentiation from HGFs to functional osteoblasts via epigenetic modification and osteogenic signaling with bone morphogenetic protein 2 (BMP2) in vitro and in vivo. HGF treatment with 5-aza-2'-deoxycytidine (5-aza-dC) induced demethylation in the hypermethylated CpG islands of the osteogenic lineage marker genes RUNX2 and ALP, and subsequent BMP2 treatment successfully drove the fibroblasts to the osteoblasts' lineage...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28077088/integrated-rna-seq-and-dnase-seq-analyses-identify-phenotype-specific-bmp4-signaling-in-breast-cancer
#2
M Ampuja, T Rantapero, A Rodriguez-Martinez, M Palmroth, E L Alarmo, M Nykter, A Kallioniemi
BACKGROUND: Bone morphogenetic protein 4 (BMP4) plays an important role in cancer pathogenesis. In breast cancer, it reduces proliferation and increases migration in a cell line-dependent manner. To characterize the transcriptional mediators of these phenotypes, we performed RNA-seq and DNase-seq analyses after BMP4 treatment in MDA-MB-231 and T-47D breast cancer cells that respond to BMP4 with enhanced migration and decreased cell growth, respectively. RESULTS: The RNA-seq data revealed gene expression changes that were consistent with the in vitro phenotypes of the cell lines, particularly in MDA-MB-231, where migration-related processes were enriched...
January 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28075462/dnalk2-inhibits-the-proliferation-and-invasiveness-of-breast-cancer-mda-mb-231-cells-through-the-smad-dependent-pathway
#3
Ke Wang, Xiaoxiao Sun, Hong Lei Feng, Chang Fei, Yan Zhang
Breast cancer is one of the most common malignant neoplasms diagnosed in females worldwide. Bone morphogenetic proteins (BMPs), which belong to the TGF-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration and apoptosis in breast cancer. BMPs can bind to type I and II serine/threonine kinase receptors to regulate cell proliferation, invasion, migration, and apoptosis. Type I receptors are expressed in various breast cancer cell lines and primary tumor samples...
December 30, 2016: Oncology Reports
https://www.readbyqxmd.com/read/28069901/bmp15-regulates-the-inhibin-activin-system-independently-of-ovulation-rate-control-in-sheep
#4
Anthony Estienne, Belén Lahoz, Peggy Jarrier, Loys Bodin, José Folch, José Luis Alabart, Stephane Fabre, Danielle Monniaux
Polymorphisms in the gene encoding bone morphogenetic protein 15 (BMP15) have been associated with multiple ovulations in sheep. As BMP15 regulates inhibin expression in rodents, we assumed that the ovarian inhibin/activin system could mediate part of the effect of BMP15 mutations in the regulation of ovulation rate in sheep. To answer this question, we have studied the effects of two natural loss-of-function mutations of BMP15 on the expression of components of this system. The FecX(R) and the FecX(Gr) mutations, when present respectively in Rasa Aragonesa ewes at the heterozygous state and in Grivette ewes at the homozygous state, were associated with a two-fold increase in ovulation rate...
January 9, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28069556/regeneration-of-bone-using-nanoplex-delivery-of-fgf-2-and-bmp-2-genes-in-diaphyseal-long-bone-radial-defects-in-a-diabetic-rabbit-model
#5
Behnoush Khorsand, Nate Nicholson, Anh-Vu Do, John E Femino, James A Martin, Emily Petersen, Brian Guetschow, Douglas C Fredericks, Aliasger K Salem
Bone fracture healing impairment related to systemic diseases such as diabetes can be addressed by growth factor augmentation. We previously reported that growth factors such as fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) work synergistically to encourage osteogenesis in vitro. In this report, we investigated if BMP-2 and FGF-2 together can synergistically promote bone repair in a leporine model of diabetes mellitus, a condition that is known to be detrimental to union. We utilized two kinds of plasmid DNA encoding either BMP-2 or FGF-2 formulated into polyethylenimine (PEI) complexes...
January 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28068493/bmp1-and-tll1-are-required-for-maintaining-periodontal-homeostasis
#6
J Wang, D Massoudi, Y Ren, A M Muir, S E Harris, D S Greenspan, J Q Feng
Mutations in bone morphogenetic protein 1 (BMP1) in humans or deletion of BMP1 and related protease tolloid like 1 (TLL1) in mice lead to osteogenesis imperfecta (OI). Here, we show progressive periodontal defects in mice in which both BMP1 and TLL1 have been conditionally ablated, including malformed periodontal ligament (PDL) (recently shown to play key roles in normal alveolar bone formation), significant loss in alveolar bone mass ( P < 0.01), and a sharp reduction in cellular cementum. Molecular mechanism studies revealed a dramatic increase in the uncleaved precursor of type I collagen (procollagen I) and a reduction in dentin matrix protein 1 (DMP1), which is partially responsible for defects in extracellular matrix (ECM) formation and mineralization...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28068481/micrornas-and-periodontal-homeostasis
#7
X Luan, X Zhou, J Trombetta-eSilva, M Francis, A K Gaharwar, P Atsawasuwan, T G H Diekwisch
MicroRNAs (miRNAs) are a group of small RNAs that control gene expression in all aspects of eukaryotic life, primarily through RNA silencing mechanisms. The purpose of the present review is to introduce key miRNAs involved in periodontal homeostasis, summarize the mechanisms by which they affect downstream genes and tissues, and provide an introduction into the therapeutic potential of periodontal miRNAs. In general, miRNAs function synergistically to fine-tune the regulation of biological processes and to remove expression noise rather than by causing drastic changes in expression levels...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28068334/two-paralogous-tetraspanins-tsp-12-and-tsp-14-function-with-the-adam10-metalloprotease-sup-17-to-promote-bmp-signaling-in-caenorhabditis-elegans
#8
Lin Wang, Zhiyu Liu, Herong Shi, Jun Liu
The highly conserved bone morphogenetic protein (BMP) signaling pathway regulates many developmental and homeostatic processes. While the core components of the BMP pathway have been well studied, much research is needed for understanding the mechanisms involved in the precise spatiotemporal control of BMP signaling in vivo. Here, we provide evidence that two paralogous and evolutionarily conserved tetraspanins, TSP-12 and TSP-14, function redundantly to promote BMP signaling in C. elegans. We further show that the ADAM10 (a disintegrin and metalloprotease 10) ortholog SUP-17 also functions to promote BMP signaling, and that TSP-12 can bind to and promote the cell surface localization of SUP-17...
January 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28067796/combined-effects-of-androgen-and-growth-hormone-on-osteoblast-marker-expression-in-mouse-c2c12-and-mc3t3-e1-cells-induced-by-bone-morphogenetic-protein
#9
Kosuke Kimura, Tomohiro Terasaka, Nahoko Iwata, Takayuki Katsuyama, Motoshi Komatsubara, Ryota Nagao, Kenichi Inagaki, Fumio Otsuka
Osteoblasts undergo differentiation in response to various factors, including growth factors and steroids. Bone mass is diminished in androgen- and/or growth hormone (GH)-deficient patients. However the functional relationship between androgen and GH, and their combined effects on bone metabolism, remains unclear. Here we investigated the mutual effects of androgen and GH on osteoblastic marker expression using mouse myoblastic C2C12 and osteoblast-like MC3T3-E1 cells. Combined treatment with dihydrotestosterone (DHT) and GH enhanced BMP-2-induced expression of Runx2, ALP, and osteocalcin mRNA, compared with the individual treatments in C2C12 cells...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28064277/smad2-phosphorylation-in-diabetic-kidney-tubule-epithelial-cells-is-associated-with-modulation-of-several-transforming-growth-factor-%C3%AE-family-members
#10
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
BACKGROUND: The role of transforming growth factor-β (TGF-β) has recently gained much attention in diabetic nephropathy and kidney fibrosis. In this study, we extend this to an assessment of transcriptional regulation of the entire TGF-β superfamily in kidneys from diabetic vs. healthy mice. In order to study the translation between mouse model and patients, we evaluated the signature of phosphorylated Sma- and Mad-related protein 2 (pSmad2), as molecular marker of TGF-β/activin activity, in the kidneys of streptozotocin (STZ)-treated mice compared to that of type 1 diabetes (T1D) patients...
January 7, 2017: Nephron
https://www.readbyqxmd.com/read/28062564/tgf-%C3%AE-bone-morphogenetic-protein-and-activin-signaling-and-the-tumor-microenvironment
#11
Michael W Pickup, Philip Owens, Harold L Moses
The cellular and noncellular components surrounding the tumor cells influence many aspects of tumor progression. Transforming growth factor β (TGF-β), bone morphogenetic proteins (BMPs), and activins have been shown to regulate the phenotype and functions of the microenvironment and are attractive targets to attenuate protumorigenic microenvironmental changes. Given the pleiotropic nature of the cytokines involved, a full understanding of their effects on numerous cell types in many contexts is necessary for proper clinical intervention...
January 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28062213/anti-fibrotic-effects-of-bone-morphogenetic-protein-7-modified-bone-marrow-mesenchymal-stem-cells-on-silica-induced-pulmonary-fibrosis
#12
Xiaoli Li, Guoliang An, Yan Wang, Di Liang, Zhonghui Zhu, Ximeng Lian, Piye Niu, Caixia Guo, Lin Tian
Silicosis is an occupational lung disease caused by exposure to small particles of crystalline silica, which ultimately results in diffuse pulmonary fibrosis. Evidence indicates an anti-fibrotic role of bone morphogenetic protein-7 (BMP-7) and bone marrow mesenchymal stem cells (BMSCs) in lung diseases. Therefore, strategies incorporating genetic engineering and stem cell biology might have a tremendous potential to treat critical injuries and diseases. Therefore, we modified BMSCs to overexpress the BMP-7 gene (BMP-7-BMSCs) by lentivirus transduction, and then evaluated whether fibrotic processes were inhibited by these cells in vivo...
January 4, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28060176/bone-morphogenetic-proteins-in-pediatric-spinal-arthrodesis-a-statewide-analysis-of-trends-and-outcome-of-utilization
#13
Benedict U Nwachukwu, William W Schairer, Ting Pan, Roger F Widmann, John S Blanco, Daniel W Green, Stephen Lyman, Emily R Dodwell
INTRODUCTION: Bone morphogenetic protein (BMP) is considered off-label when used to augment spinal arthrodesis in children and adolescents. There is a paucity of longer-term information on BMP use in this population. The purpose of this study was to determine the rate of BMP utilization in pediatric spinal arthrodesis, assess factors associated with BMP use in this population, and evaluate long-term outcome. METHODS: Spinal arthrodeses in patients 18 years and younger performed in New York State between 2004 and 2014 were identified through the Statewide Planning and Research Cooperative System database...
January 5, 2017: Journal of Pediatric Orthopedics
https://www.readbyqxmd.com/read/28059064/bmp-restricts-stemness-of-intestinal-lgr5-stem-cells-by-directly-suppressing-their-signature-genes
#14
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/28057877/previous-miscarriages-and-gli2-are-associated-with-anorectal-malformations-in-offspring
#15
Romy van de Putte, Charlotte H W Wijers, Ivo de Blaauw, Carlo L M Marcelis, Cornelius E J Sloots, Alice S Brooks, Paul M A Broens, Nel Roeleveld, Loes F M van der Zanden, Iris A L M van Rooij
STUDY QUESTION: Are anorectal malformations (ARMs) associated with previous miscarriages or single nucleotide polymorphisms (SNPs) in the Bone Morphogenetic Protein 4 (BMP4) and GLI family zinc finger 2 (GLI2) genes? SUMMARY ANSWER: The SNP rs3738880 in GLI2 and miscarriages were associated with ARM, especially in patients with multiple congenital anomalies (MCA). WHAT IS KNOWN ALREADY: ARM are one of the most common birth defects of the gastrointestinal tract...
January 5, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28054585/osseous-differentiation-of-human-fat-tissue-grafts-from-tissue-engineering-to-tissue-differentiation
#16
Maryna Bondarava, Chiara Cattaneo, Bin Ren, Wolfgang E Thasler, Volkmar Jansson, Peter E Müller, Oliver B Betz
Conventional bone tissue engineering approaches require isolation and in vitro propagation of autologous cells, followed by seeding on a variety of scaffolds. Those protracted procedures impede the clinical applications. Here we report the transdifferentiation of human fat tissue fragments retrieved from subcutaneous fat into tissue with bone characteristics in vitro without prior cell isolation and propagation. 3D collagen-I cultures of human fat tissue were cultivated either in growth medium or in osteogenic medium (OM) with or without addition of Bone Morphogenetic Proteins (BMPs) BMP-2, BMP-7 or BMP-9...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28054333/bmp-2-coated-mineral-coated-microparticles-improve-bone-repair-in-atrophic-non-unions
#17
M Orth, N J Kruse, B J Braun, C Scheuer, J H Holstein, A Khalil, X Yu, W L Murphy, T Pohlemann, M W Laschke, M D Menger
Atrophic non-unions are a major clinical problem. Mineral coated microparticles (MCM) are electrolyte-coated hydroxyapatite particles that have been shown in vitro to bind growth factors electrostatically and enable a tuneable sustained release. Herein, we studied whether MCM can be used in vivo to apply Bone Morphogenetic Protein-2 (BMP-2) to improve bone repair of atrophic non-unions. For this purpose, atrophic non-unions were induced in femurs of CD-1 mice (n = 48). Animals either received BMP-2-coated MCM (MCM + BMP; n = 16), uncoated MCM (MCM; n = 16) or no MCM (NONE; n = 16)...
January 2, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28052093/bone-morphogenetic-protein-9-enhances-osteogenic-differentiation-of-human-periodontal-ligament-stem-cells-via-the-jnk-pathway
#18
Pei Wang, Yanen Wang, Weizhong Tang, Xingxing Wang, Yanan Pang, Su Yang, Yibo Wei, Haochen Gao, Dalin Wang, Zhizhong Cao
Bone morphogenetic protein-9 (BMP9) shows great osteoinductive potential in bone regeneration. Periodontal ligament stem cells (PDLSCs) with multi-differentiation capability and low immunogenicity are increasingly used as seed cells for periodontal regenerative therapies. In the present study, we investigated the potent osteogenic activity of BMP9 on human PDLSCs (hPDLSCs), in which the c-Jun N-terminal kinase (JNK) pathway is possibly involved. Our results showed that JNK inhibition by the specific inhibitor SP600125 or adenovirus expressing small interfering RNA (siRNA) targeting JNK (AdR-si-JNK) significantly decreased BMP9-induced gene and protein expression of early and late osteogenic markers, such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN), in hPDLSCs...
2017: PloS One
https://www.readbyqxmd.com/read/28051358/controlled-retention-of-bmp-2-derived-peptide-on-nanofibers-based-on-mussel-inspired-adhesion-for-bone-formation
#19
Jinkyu Lee, Sajeesh Kumar Mp, Taufiq Ahmad, Min Suk Lee, Heeseok Yang, Do-Gyoon Kim, Kyobum Kim, Bosun Kwon, Heungsoo Shin
Although bone morphogenetic protein-2 (BMP-2) has been frequently used to stimulate bone formation, it has several side effects to be addressed, including the difficulty in optimization of clinically relevant doses and unwanted induction of cancerous signaling processes. In this study, an osteogenic peptide (OP) derived from BMP-2 was investigated as a substitute for BMP-2. In vitro studies showed that OP was able to enhance in the osteogenic differentiation and mineralization of human mesenchymal stem cells (hMSCs)...
January 4, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28043948/angptl2-expression-in-the-intestinal-stem-cell-niche-controls-epithelial-regeneration-and-homeostasis
#20
Haruki Horiguchi, Motoyoshi Endo, Kohki Kawane, Tsuyoshi Kadomatsu, Kazutoyo Terada, Jun Morinaga, Kimi Araki, Keishi Miyata, Yuichi Oike
The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Dysregulation of intestinal epithelial homeostasis leads to severe inflammatory bowel disease. Additionally, aberrant signaling by the secreted protein angiopoietin-like protein 2 (ANGPTL2) causes chronic inflammation in a variety of diseases. However, little is known about the physiologic role of ANGPTL2 in normal tissue homeostasis and during wound repair following injury. Here, we assessed ANGPTL2 function in intestinal physiology and disease in vivo Although intestinal development proceeded normally in Angptl2-deficient mice, expression levels of the intestinal stem cell (ISC) marker gene Lgr5 decreased, which was associated with decreased transcriptional activity of β-catenin in Angptl2-deficient mice...
January 2, 2017: EMBO Journal
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