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https://www.readbyqxmd.com/read/28105966/a-novel-approach-for-pathway-analysis-of-gwas-data-highlights-role-of-bmp-signaling-and-muscle-cell-differentiation-in-colorectal-cancer-susceptibility
#1
Aniket Mishra, Stuart MacGregor
Genome-wide association studies (GWAS) have revolutionized the field of gene mapping. As the GWAS field matures, it is becoming clear that for many complex traits, a proportion of the missing heritability is attributable to common variants of individually small effect. Detecting these small effects individually can be difficult, and statistical power would be increased if relevant variants could be grouped together for testing. Here, we propose a VEGAS2Pathway approach that aggregates association strength of individual markers into pre-specified biological pathways...
February 2017: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
https://www.readbyqxmd.com/read/28104917/overexpression-of-bone-morphogenetic-protein-3b-bmp-3b-in-adipose-tissues-protects-against-high-fat-diet-induced-obesity
#2
J Hino, M Nakatani, Y Arai, K Tsuchida, M Shirai, M Miyazato, K Kangawa
BACKGROUND: Bone morphogenetic protein-3b (BMP-3b) is a member of the transforming growth factor-β superfamily and has several activities that differ from those of other BMPs. We previously found that BMP-3b is highly expressed in adipocytes, its level is increased during obesity, and it inhibits adipogenesis by suppressing peroxisome proliferator-activated receptor γ (PPARγ) in vitro. However, the function of BMP-3b in adipose tissues in vivo remains unknown. METHODS: To determine the role of BMP-3b overexpression in adipose tissues in vivo, we generated transgenic mice (BMP-3b Tg) by using a conditional overexpression approach in fatty acid binding protein 4 (FABP4)-expressing adipocytes...
January 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28104757/analysis-and-identification-of-the-grem2-heparin-heparan-sulfate-binding-motif
#3
Chandramohan Kattamuri, Kristof Nolan, Thomas B Thompson
Bone Morphogenetic Proteins (BMP) are regulated by extracellular antagonists of the DAN (differential screening selected gene aberrative in neuroblastoma) family. Similar to the BMP ligands, certain DAN family members have been shown to interact with heparin and heparan sulfate (HS). Structural studies of DAN family members Gremlin-1 and Gremlin-2 have revealed a dimeric growth-factor like fold where a series of lysine residues cluster along one face of the protein. In this study, we used mutagenesis, heparin binding measurements, and cell surface binding analysis to identify lysine residues that are important for heparin/HS binding in Gremlin-2...
January 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28103529/improving-osteogenesis-of-three-dimensional-porous-scaffold-based-on-mineralized-recombinant-human-like-collagen-via-mussel-inspired-polydopamine-and-effective-immobilization-of-bmp-2-derived-peptide
#4
Jing Zhou, Xiaodong Guo, Qixin Zheng, Yongchao Wu, Fuzai Cui, Bin Wu
An ideal bone substitute should be biocompatible, biodegradable, osteoinductive and osteoconductive. In our previous work, we fabricated a three-dimensional porous scaffold based on mineralized recombinant human-like collagen, nano-hydroxyapatite/recombinant human-like collagen/poly(lactic acid) (nHA/RHLC/PLA). Like other HA/collagen scaffolds, the nHA/RHLC/PLA scaffold lacked osteoinductive bioactivity. The purpose of the present study was to develop a polydopamine (pDA)-assisted BMP-2-derived peptide (designated as P24) surface modification strategy for improving the osteogenesis of the nHA/RHLC/PLA scaffold...
January 4, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28102712/bone-morphogenetic-protein-2-and-7-mediate-the-anabolic-function-of-nucleus-pulposus-cells-with-discrete-mechanisms
#5
Victor Yl Leung, Lixiong Zhou, Wai-Kit Tam, Yi Sun, Fengjuan Lv, Guangqian Zhou, Kenneth Mc Cheung
Bone morphogenetic proteins (BMPs) play roles in promoting cell anabolism, especially extracellular matrix production. The difference between BMP members in their capacity to modulate intervertebral disc cell activity is yet to be defined. BMP-7/OP-1 has been shown to retard disc degeneration. We compared the activity of BMP-7 with BMP-2 on nucleus pulposus (NP) cell phenotype and function, and investigated how they differentially affect the gene expression profiles of signaling cascade components in human NP cells under degenerative states...
January 19, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28100499/gremlin1-plays-a-key-role-in-kidney-development-and-renal-fibrosis
#6
Rachel H Church, Imran Ali, Mitchel Tate, Deborah Lavin, Arjun Krishnakumar, Helena M Kok, Roel Goldschmeding, Finian Martin, Derek Brazil
Grem1, an antagonist of bone morphogenetic proteins, plays a key role in embryogenesis. A highly specific temporospatial gradient of Grem1 and BMP signalling is critical to normal lung, kidney and limb development. Grem1 levels are increased in renal fibrotic conditions including acute kidney injury, diabetic nephropathy, chronic allograft nephropathy and immune glomerulonephritis. A small number of grem1-/- whole body knockout mice on a mixed genetic background (8 %) are viable, with a single, enlarged left kidney and grossly normal histology...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28098740/adult-scoliosis-deformity-surgery-comparison-of-outcomes-between-1-vs-2-attending-surgeons
#7
Jaime A Gomez, Virginie Lafage, Daniel M Scuibba, Shay Bess, Gregory M Mundis, Barthelemy Liabaud, Regina Hanstein, Christopher Shaffrey, Michael Kelly, Christopher Ames, Justin S Smith, Peter G Passias, Thomas Errico, Frank Schwab
STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: Assess outcomes of adult spinal deformity (ASD) surgery performed by 1 vs. 2 attending surgeons. SUMMARY OF BACKGROUND DATA: ASD centers have developed 2-attending teams in order to improve efficiency; their effects on complications and outcomes have not been reported. METHODS: ASD patients with ≥5 levels fused and > 2-year follow-up were included...
January 16, 2017: Spine
https://www.readbyqxmd.com/read/28095523/effects-of-titanium-surface-microtopography-and-simvastatin-on-growth-and-osteogenic-differentiation-of-human-mesenchymal-stem-cells-in-estrogen-deprived-cell-culture
#8
Premjit Arpornmaeklong, Prisana Pripatnanont, Chonticha Chookiatsiri, Boonsin Tangtrakulwanich
PURPOSE: This study aimed to investigate the effects of titanium surface topography and simvastatin on growth and osteogenic differentiation of human bone marrow stromal cells (hBMSCs) in estrogen-deprived (ED) cell culture. MATERIALS AND METHODS: Human BMSCs were seeded on cell culture plates, smooth-surface titanium (Ti) disks, and sandblasted with large grits and acid etched (SLA)-surface Ti disks; and subsequently cultured in regular (fetal bovine serum [FBS]), ED, and ED-with 100 nM simvastatin (ED-SIM) culture media for 14 to 21 days...
January 2017: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/28094870/igf1r-signaling-acts-on-the-anagen-to-catagen-transition-in-the-hair-cycle
#9
Mathieu Castela, Fabien Linay, Edwige Roy, Philippe Moguelet, Jie Xu, Martin Holzenberger, Kiarash Khosrotehrani, Selim Aractingi
Insulin like growth factor 1 (IGF1) is important for skin development and homeostasis. However, overexpression and inactivation studies have produced variable findings regarding its role in hair follicle (HF) biology. Here, we studied a conditional and inducible knockout of the IGF1 receptor (IGF1R) in keratin 15-expressing bulge cells. Deletion of IGF1R after the development of the skin appendages in K15-IGF1R(KO) mice showed no abnormalities in epidermal homeostasis. Numbers of bulge cells were lower in K15-IGF1R(KO) mice than in controls, without consequences on wound healing, at least in young mice...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28094240/ectopic-bone-formation-by-gel-derived-bioactive-glass-poly-l-lactide-co-glycolide-composites-in-a-rabbit-muscle-model
#10
Joanna Filipowska, Katarzyna Cholewa-Kowalska, Jarosław Wieczorek, Danuta Semik, Zbigniew Dąbrowski, Maria Łączka, Anna M Osyczka
In this study we aimed to assess the in vivo osteoinductive properties of two composite scaffolds made of PLGA (poly-L-lactide-co-glycolide) and two types of gel-derived bioactive glasses, namely a high silica S2 bioactive glass (S2-PLGA composites) or high lime A2 bioactive glass (A2-PLGA composites). To achieve that, the potential of the composites to induce ectopic bone formation in a rabbit muscle has been examined along with the control PLGA scaffold. Cylinder-like scaffolds of 7  ×  3 mm (width  ×  height) were implanted into pouches created in the latissimus dorsi muscle of 18 New Zealand rabbits...
January 17, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28093887/collagen-hydrogel-scaffold-promotes-mesenchymal-stem-cell-and-endothelial-cell-coculture-for-bone-tissue-engineering
#11
Bao-Ngoc B Nguyen, Rebecca A Moriarty, Tim Kamalitdinov, Julie M Etheridge, John P Fisher
The generation of functional, vascularized tissues is a key challenge for the field of tissue engineering. Before clinical implantations of such tissue engineered bone constructs can succeed, tactics to promote neovascularization need to be strengthened. We have previously demonstrated that the tubular perfusion system (TPS) bioreactor is an effective culturing method to augment osteogenic differentiation and maintain viability of human mesenchymal stem cells (hMSC). Here, we devised a strategy to address the need for a functional microvasculature by designing an in vitro coculture system that simultaneously cultures osteogenic differentiating hMSCs with endothelial cells (ECs)...
January 17, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28090303/genotype-phenotype-effects-of-bmpr2-mutations-on-disease-severity-in-mouse-models-of-pulmonary-hypertension
#12
Andrea L Frump, Arunima Datta, Sampa Ghose, James West, Mark P de Caestecker
More than 350 mutations in the type-2 BMP (bone morphogenetic protein) receptor, BMPR2, have been identified in patients with heritable pulmonary arterial hypertension (HPAH). However, only 30% of BMPR2 mutation carriers develop PAH, and we cannot predict which of these carriers will develop clinical disease. One possibility is that the nature of the BMPR2 mutation affects disease severity. This hypothesis has been difficult to test clinically, given the rarity of HPAH and the complexity of the confounding genetic and environmental risk factors...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28087378/new-scaffolds-encapsulating-tgf-%C3%AE-3-bmp-7-combinations-driving-strong-chondrogenic-differentiation
#13
Jose Crecente-Campo, Erea Borrajo, Anxo Vidal, Marcos Garcia-Fuentes
The regeneration of articular cartilage remains an unresolved question despite the current access to a variety of tissue scaffolds activated with growth factors relevant to this application. Further advances might result from combining more than one of these factors; here, we propose a scaffold composition optimized for the dual delivery of BMP-7 and TGF-β3, two proteins with described chondrogenic activity. First, we tested in a mesenchymal stem cell micromass culture with TGF-β3 whether the exposure to microspheres loaded with BMP-7 would improve cartilage formation...
January 10, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28084316/tnf%C3%AE-drives-pulmonary-arterial-hypertension-by-suppressing-the-bmp-type-ii-receptor-and-altering-notch-signalling
#14
Liam A Hurst, Benjamin J Dunmore, Lu Long, Alexi Crosby, Rafia Al-Lamki, John Deighton, Mark Southwood, Xudong Yang, Marko Z Nikolic, Blanca Herrera, Gareth J Inman, John R Bradley, Amer A Rana, Paul D Upton, Nicholas W Morrell
Heterozygous germ-line mutations in the bone morphogenetic protein type-II receptor (BMPR-II) gene underlie heritable pulmonary arterial hypertension (HPAH). Although inflammation promotes PAH, the mechanisms by which inflammation and BMPR-II dysfunction conspire to cause disease remain unknown. Here we identify that tumour necrosis factor-α (TNFα) selectively reduces BMPR-II transcription and mediates post-translational BMPR-II cleavage via the sheddases, ADAM10 and ADAM17 in pulmonary artery smooth muscle cells (PASMCs)...
January 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28083909/increased-plekho1-within-osteoblasts-suppresses-smad-dependent-bmp-signaling-to-inhibit-bone-formation-during-aging
#15
Jin Liu, Chao Liang, Baosheng Guo, Xiaohao Wu, Defang Li, Zongkang Zhang, Kang Zheng, Lei Dang, Xiaojuan He, Changwei Lu, Songlin Peng, Xiaohua Pan, Bao-Ting Zhang, Aiping Lu, Ge Zhang
Emerging evidence indicates that the dysregulation of protein ubiquitination plays a crucial role in aging-associated diseases. Smad-dependent canonical BMP signaling pathway is indispensable for osteoblastic bone formation, which could be disrupted by the ubiquitination and subsequent proteasomal degradation of Smad1/5, the key molecules for BMP signaling transduction. However, whether the dysregulation of Smad1/5 ubiquitination and disrupted BMP signaling pathway is responsible for the age-related bone formation reduction is still underexplored...
January 13, 2017: Aging Cell
https://www.readbyqxmd.com/read/28082076/topical-bisphosphonate-augments-fixation-of-bone-grafted-hydroxyapatite-coated-implants-bmp-2-causes-resorption-based-decrease-in-bone
#16
Jorgen Baas, Marianne Vestermark, Thomas Jensen, Joan Bechtold, Kjeld Soballe, Thomas Jakobsen
Bone allograft is used in total joint arthroplasties in order to enhance implant fixation. BMPs are known to stimulate new bone formation within allograft, but also known to accelerate graft resorption. Bisphosphonates are strong inhibitor of bone resorption. The aim of this study was to investigate whether the bisphosphonate zoledronate was able to counteract the accelerated graft resorption without interfering with the BMP induced bone formation. In the present study the two drugs alone and in combination were studied in our canine model of impaction bone grafting...
January 7, 2017: Bone
https://www.readbyqxmd.com/read/28076890/suppression-of-osteogenic-activity-by-regulation-of-wnt-and-bmp-signaling-during-titanium-particle-induced-osteolysis
#17
Ju-Suk Nam, Ashish Ranjan Sharma, Supriya Jagga, Dong-Hyun Lee, Garima Sharma, Lich Thi Nguyen, Yeon Hee Lee, Jun-Dong Chang, Chiranjib Chakraborty, Sang-Soo Lee
Periprosthetic osteolysis remains the leading obstacle for total joint replacements. Primarily, it was thought that aseptic loosening is mainly caused by macrophage mediated inflammatory process arising from production of wear debris. The role of osteoclasts and its sequential bone resorption ability has been extensively studied, but little is known about impaired osteogenesis during osteolysis. In the current study, we have tried to delineate the regulatory mechanism of osteogenic signals by Ti particles in osteoprogenitor cells as well its participatory role in wear debris induced osteolysis...
January 11, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28074350/a-comparative-study-of-the-bone-regenerative-effect-of-chemically-modified-rna-encoding-bmp-2-or-bmp-9
#18
Behnoush Khorsand, Satheesh Elangovan, Liu Hong, Alexander Dewerth, Michael S D Kormann, Aliasger K Salem
Employing cost-effective biomaterials to deliver chemically modified ribonucleic acid (cmRNA) in a controlled manner addresses the high cost, safety concerns, and lower transfection efficiency that exist with protein and gene therapeutic approaches. By eliminating the need for nuclear entry, cmRNA therapeutics can potentially overcome the lower transfection efficiencies associated with non-viral gene delivery systems. Here, we investigated the osteogenic potential of cmRNA-encoding BMP-9, in comparison to cmRNA-encoding BMP-2...
January 10, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28071602/microgrooved-topographical-surface-directs-tenogenic-lineage-specific-differentiation-of-mouse-tendon-derived-stem-cells
#19
Yuan Shi, Kaili Zhou, Wenjie Zhang, Zhiyong Zhang, Guangdong Zhou, Yilin Cao, Wei Liu
Tendon derived stem cells (TDSCs) are the endogenous cell source for tenocyte turnover and tendon functional maintenance. They are also the important cell source for tendon engineering and regeneration. In addition, TDSCs also play an important role in tendinopathy via their non-tenogenic lineage differentiation. It has been well demonstrated that cell shape could determine mesenchymal stem cell (MSC) lineage differentiation. In this study, a parallel microgrooved polydimethylsiloxane (PDMS) membrane (10 µm groove width and 3 µm depth) was employed to investigate the role of cell elongation via this particular topographic surface in directing murine TDSC (mTDSC) lineage differentiation...
January 10, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28069701/loss-of-axin2-results-in-impaired-heart-valve-maturation-and-subsequent-myxomatous-valve-disease
#20
Alexia Hulin, Vicky Moore, Jeanne M James, Katherine E Yutzey
AIMS: Myxomatous valve disease (MVD) is the most common aetiology of primary mitral regurgitation. Recent studies suggest that defects in heart valve development can lead to heart valve disease in adults. Wnt/β-catenin signalling is active during heart valve development and has been reported in human MVD. The consequences of increased Wnt/β-catenin signalling due to Axin2 deficiency in postnatal valve remodelling and pathogenesis of MVD were determined. METHODS AND RESULTS: To investigate the role of Wnt/β-catenin signalling, we analysed heart valves from mice deficient in Axin2 (KO), a negative regulator of Wnt/β-catenin signalling...
January 2017: Cardiovascular Research
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