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https://www.readbyqxmd.com/read/28095466/substrate-stiffness-controls-osteoblastic-and-chondrocytic-differentiation-of-mesenchymal-stem-cells-without-exogenous-stimuli
#1
Rene Olivares-Navarrete, Erin M Lee, Kathryn Smith, Sharon L Hyzy, Maryam Doroudi, Joseph K Williams, Ken Gall, Barbara D Boyan, Zvi Schwartz
Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA) polymer surfaces with elastic moduli ranging from 0...
2017: PloS One
https://www.readbyqxmd.com/read/28094446/deep-sequencing-of-a-candidate-region-harboring-the-sox9-gene-for-the-canine-xx-disorder-of-sex-development
#2
J Nowacka-Woszuk, I Szczerbal, H Pausch, S Hundi, M K Hytönen, A Grzemski, K Flisikowski, H Lohi, M Switonski, M Szydlowski
A disorder of sex development (DSD) in dogs with female sex chromosomes (78, XX), a lack of the SRY gene and the presence of testes or ovotestes is commonly diagnosed in numerous breeds. The molecular background of DSD is not fully recognized but has been linked to the copy number variation in the region harboring the SOX9 gene. We applied a genome-wide association study and targeted next-generation sequencing techniques to compare DSD and normal female dogs. The genome-wide association study did not indicate a significant chromosome region...
January 17, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28087486/enhanced-articular-cartilage-by-human-mesenchymal-stem-cells-in-enzymatically-mediated-transiently-rgds-functionalized-collagen-mimetic-hydrogels
#3
Paresh A Parmar, Jean-Philippe St-Pierre, Lesley W Chow, Christopher D Spicer, Violet Stoichevska, Yong Y Peng, Jerome A Werkmeister, John A M Ramshaw, Molly M Stevens
: Recapitulation of the articular cartilage microenvironment for regenerative medicine applications faces significant challenges due to the complex and dynamic biochemical and biomechanical nature of native tissue. Towards the goal of biomaterial designs that enable the temporal presentation of bioactive sequences, recombinant bacterial collagens such as Streptococcal collagen-like 2 (Scl2) proteins can be employed to incorporate multiple specific bioactive and biodegradable peptide motifs into a single construct...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087378/new-scaffolds-encapsulating-tgf-%C3%AE-3-bmp-7-combinations-driving-strong-chondrogenic-differentiation
#4
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/28070687/predicting-chromatin-architecture-from-models-of-polymer-physics
#5
REVIEW
Simona Bianco, Andrea M Chiariello, Carlo Annunziatella, Andrea Esposito, Mario Nicodemi
We review the picture of chromatin large-scale 3D organization emerging from the analysis of Hi-C data and polymer modeling. In higher mammals, Hi-C contact maps reveal a complex higher-order organization, extending from the sub-Mb to chromosomal scales, hierarchically folded in a structure of domains-within-domains (metaTADs). The domain folding hierarchy is partially conserved throughout differentiation, and deeply correlated to epigenomic features. Rearrangements in the metaTAD topology relate to gene expression modifications: in particular, in neuronal differentiation models, topologically associated domains (TADs) tend to have coherent expression changes within architecturally conserved metaTAD niches...
January 9, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28069701/loss-of-axin2-results-in-impaired-heart-valve-maturation-and-subsequent-myxomatous-valve-disease
#6
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
https://www.readbyqxmd.com/read/28069589/analysis-of-the-fgfr2c342y-mouse-model-shows-condensation-defects-due-to-misregulation-of-sox9-expression-in-prechondrocytic-mesenchyme
#7
Emma Peskett, Samin Kumar, William Baird, Janhvi Jaiswal, Ming Li, Priyanca Patel, Jonathan A Britto, Erwin Pauws
Syndromic craniosynostosis caused by mutations in FGFR2 is characterised by developmental pathology in both endochondral and membranous skeletogenesis. Detailed phenotypic characterisation of features in the membranous calvarium, the endochondral cranial base and other structures in the axial and appendicular skeleton has not been performed at embryonic stages. We investigated bone development in the Crouzon mouse model (Fgfr2(C342Y)) at pre- and post-ossification stages to improve understanding of the underlying pathogenesis...
January 9, 2017: Biology Open
https://www.readbyqxmd.com/read/28068523/rs12941170-at-sox9-gene-associated-with-orofacial-clefts-in-chinese
#8
Zhong-Lin Jia, Sha He, Shu-Yuan Jiang, Bi-He Zhang, Shi-Jun Duan, Jia-Yu Shi, Ning Huang, Wen-Chao Zhu, Bing Shi
OBJECTIVE: Non-syndromic orofacial cleftings (NSOCs) are considered as complex trait, which results from genetic and/or environmental modifiers. Current findings could only explain small portion of the NSOCs. SOX9 gene plays an important role during craniofacial development in animal models and the Pierre Robin sequence (PRS). However, its role in non-syndromic clefts remains unknown. DESIGN: In this study, we selected eight SNPs in and around SOX9 gene to make maximum coverage, and genotyped them by using RFLP-PCR and ligase detection reaction (LDR) methods to test its associations among 151 NSOCs (53 NSCLP, 52 NSCLO and 46 NSCPO) from Western Han Chinese population...
December 30, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/28064441/analysis-of-the-origin-of-anaplastic-pancreatic-cancer-and-the-mechanism-of-its-dedifferentiation
#9
Kotaro Miura, Kenjiro Kimura, Ryosuke Amano, Sadaaki Yamazoe, Go Ohira, Kohei Nishio, Naoki Kametani, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: We researched the origin and progression of anaplastic pancreatic cancer (APC) from the viewpoints of cell lineage, epithelial-mesenchymal transition (EMT) and cancer stem like cells (CSC). METHODS: Using specimens from patients with APC and differentiated pancreatic ductal adenocarcinoma (PDAC), expression of sex-determining region Y box 9 (SOX9), E-cadherin, vimentin, ZEB-1, Snail, N-cadherin, CD24 and CD44 was estimated using immunohistochemistry...
January 8, 2017: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/28060847/enhanced-chondrogenic-differentiation-of-human-umbilical-cord-wharton-s-jelly-derived-mesenchymal-stem-cells-by-gsk-3-inhibitors
#10
Prapot Tanthaisong, Sumeth Imsoonthornruksa, Apichart Ngernsoungnern, Piyada Ngernsoungnern, Mariena Ketudat-Cairns, Rangsun Parnpai
Articular cartilage is an avascular, alymphatic, and aneural system with very low regeneration potential because of its limited capacity for self-repair. Mesenchymal stem cells (MSCs) are the preferred choice for cell-based therapies. Glycogen synthase kinase 3 (GSK-3) inhibitors are compounds that can induce the Wnt signaling pathway, which is involved in chondrogenesis and cartilage development. Here, we investigated the influence of lithium chloride (LiCl) and SB216763 synergistically with TGF-β3 on chondrogenic differentiation in human mesenchymal stem cells derived from Wharton's jelly tissue (hWJ-MSCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28059449/irx3-and-bmp2-regulate-mouse-mesenchymal-cell-chondrogenic-differentiation-in-both-a-sox9-dependent-and-independent-manner
#11
Yoshihiro Tamamura, Kenichi Katsube, Hisashi Mera, Maki Itokazu, Shigeyuki Wakitani
Sox9, a master regulator of cartilage development, controls the cell fate decision to differentiate from mesenchymal to chondrogenic cells. In addition, Sox9 regulates the proliferation and differentiation of chondrocytes, as well as the production of cartilage-specific proteoglycans. The existence of Sox9-independent mechanisms in cartilage development remains to be determined. Here, we attempted to identify genes involved in such putative mechanisms via microarray analysis using a mouse chondrogenic cell line, N1511...
January 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28056722/hyaluronic-acid-coating-enhances-biocompatibility-of-pga-unwoven-fiber-scaffold-and-cartilage-formation
#12
Xunxun Lin, Wenbo Wang, Wen Jie Zhang, Zhi-Yong Zhang, Guangdong Zhou, Yilin Cao, Wei Liu
Synthetic polymers such as polyglycolic acid (PGA) fibers are the traditional tissue engineering scaffolds that are widely used for engineering a variety of soft tissues. However, the major disadvantage of this polymer material is its released acidic degradation products that trigger inflammatory response and fibrotic process, which affects the biocompatibility and the quality of the engineered tissues. In this study, the effect of hyaluronic acid (HA) coating on improving PGA biocompatibility was explored...
January 5, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28051157/progressive-induction-of-hepatocyte-progenitor-cells-in-chronically-injured-liver
#13
Naoki Tanimizu, Norihisa Ichinohe, Masahiro Yamamoto, Haruhiko Akiyama, Yuji Nishikawa, Toshihiro Mitaka
Differentiated epithelial cells show substantial lineage plasticity upon severe tissue injuries. In chronically injured mouse livers, part of hepatocytes become Sry-HMG box containing 9 (Sox9) (+) epithelial cell adhesion molecule (-) hepatocyte nuclear factor 4 α (+) biphenotypic hepatocytes. However, it is not clear whether all Sox9(+) hepatocytes uniformly possess cellular properties as hepatocyte progenitors. Here, we examined the microarray data comparing Sox9(+) hepatocytes with mature hepatocytes and identified CD24 as a novel marker for biphenotypic hepatocytes...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28045957/normal-levels-of-sox9-expression-in-the-developing-mouse-testis-depend-on-the-tes-tesco-enhancer-but-this-does-not-act-alone
#14
Nitzan Gonen, Alexander Quinn, Helen C O'Neill, Peter Koopman, Robin Lovell-Badge
During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28040117/skeletal-dysplasia-with-bowing-long-bones-proposed-flowchart-for-prenatal-diagnosis-with-case-demonstration
#15
Gabriele Tonni, Marcella Palmisano, Mario Lituania, Gianpaolo Grisolia, Ave Maria Baffico, Maria Paola Bonasoni, Pierpaolo Pattacini, Claudio De Felice, Edward Araujo Júnior
OBJECTIVE: Skeletal dysplasia with bowing long bones is a rare group of multiple characterized congenital anomalies. MATERIALS AND METHODS: We introduce a simple, practical diagnostic flowchart that may be helpful in identifying the appropriate pathway of obstetrical management. RESULTS: Herein, we describe four fetal cases of bent bony dysplasia that focus on ultrasound findings, phenotype, molecular tests, distinctive X-ray features, and chondral growth plate histology...
December 2016: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28030592/a-novel-missense-mutation-224g-t-r75m-in-sry-coding-region-interferes-with-nuclear-import-and-results-in-46-xy-complete-gonadal-dysgenesis
#16
Wufang Fan, Bei Wang, Shanshan He, Tengfei Zhang, Chenxing Yin, Yunping Chen, Shuqi Zheng, Jixia Zhang, Lin Li
SRY-mutation-caused sex reversal is a rare disease and mostly associated with a de novo mutation since the patients with defective SRY is infertile. There are many reports about SRY-mutation associated 46, XY ovarian disorder of sex development (DSD), but few described their molecular mechanism. Here we report a de novo mutation 224G>T (R75M) in SRY associated with a phenotypic female, 46, XY karyotype and dysgerminoma. The wild and mutated SRY were cloned into recombinant plasmid and expressed in cells in vitro, the result showed the mutated SRY is greatly accumulated in cytoplasm while the wild type SRY is mostly localized in nucleus...
2016: PloS One
https://www.readbyqxmd.com/read/28028895/characterization-of-sox9-overexpressing-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-based-engineered-cartilage-both-in-vitro-and-in-vivo
#17
Xiao-Li Li, Jun Zhang, Hua-Nan Luo, Xiaoyan Zhao, A-Ling Zhang, Zheng-Hui Wang
The source of seed cells is a critical factor for tissue engineering . The goal of this study was to evaluate the chondrogenesis of Sox9-overexpressing human umbilical cord mesenchymal stem cells (hUCMSCs) seeded onto bone matrix gelatin (BMG)/fibrin hybrid scaffolds both in vitro and in vivo. hUCMSCs were stably transfected with Sox9-expressing plasmid and grown on the three-dimensional BMG/fibrin hybrid scaffold for 8 weeks. Scanning electron microscopy and histochemistry were performed. The hUCMSC-loaded scaffolds were implanted into the subcutaneous layer of immunocompetent rats and chondrogenesis and host immune responses were monitored for 8 weeks...
December 28, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28025555/synthesis-biological-evaluation-and-docking-studies-of-a-novel-sulfonamido-based-gallate-as-pro-chondrogenic-agent-for-the-treatment-of-cartilage
#18
Xiao Lin, Ling Chai, Buming Liu, Hailan Chen, Li Zheng, Qin Liu, Cuiwu Lin
Gallic acid (GA) and its derivatives are anti-inflammatory agents and are reported to have potent effects on Osteoarthritis (OA) treatment. Nonetheless, it is generally accepted that the therapeutic effect and biocompatibility of GA is much weaker than its esters due to the high hydrophilicity. The therapeutic effect of GA on OA could be improved if certain structural modifications were made to increase its hydrophobicity. In this study, a novel sulfonamido-based gallate was synthesized by bonding sulfonamide with GA, and its biological evaluations on OA were investigated...
December 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28024939/rage-deficiency-alleviates-aortic-valve-calcification-in-apoe-mice-via-the-inhibition-of-endoplasmic-reticulum-stress
#19
Bo Wang, Zhejun Cai, Baoqing Liu, Zongtao Liu, Xianming Zhou, Nianguo Dong, Fei Li
Receptor for advanced glycation end products (RAGE) and endoplasmic reticulum (ER) stress have been shown to be involved in calcific aortic valve disease (CAVD). However, the association between RAGE and ER stress remains unknown in the pathogenesis of CAVD. The current study aims to test the hypothesis that RAGE deficiency alleviates aortic valve calcification via the inhibition of ER stress. Up-regulation of RAGE and ER stress markers in calcified human aortic valves were confirmed by immunoblotting. Aortic valve calcification was evaluated in atherosclerotic prone ApoE(-/-) mice or in mice with dual deficiencies of ApoE and RAGE (ApoE(-/-)RAGE(-/-)) fed with high cholesterol diet for 24weeks...
December 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28017821/identification-of-a-p-arg708gln-variant-in-col1a2-in-atypical-femoral-fractures
#20
Funck-Brentano Thomas, Ostertag Agnes, Debiais Francoise, Fardellone Patrice, Corinne Collet, Mornet Etienne, Cohen-Solal Martine
OBJECTIVES: Long-term bisphosphonates exposure is a proven risk factor for atypical femoral fractures (AFF) but several cases occur in untreated patients. The identification of other risk factors for AFF is critical for the management of osteoporosis. We here assessed the genetic factors associated with AFF regardless of the treatment. METHODS: Cases were identified through ICD-10 codes in 3 academic centers. Medical records were analyzed by 2 investigators that adjudicated X-rays for typical or atypical fractures...
December 22, 2016: Joint, Bone, Spine: Revue du Rhumatisme
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