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Wing Lee Chan, Magdalena Steiner, Tomasz Witkos, Johannes Egerer, Björn Busse, Shuji Mizumoto, Jan M Pestka, Haikuo Zhang, Ingrid Hausser, Layal Abo Khayal, Claus-Eric Ott, Mateusz Kolanczyk, Bettina Willie, Thorsten Schinke, Chiara Paganini, Antonio Rossi, Kazuyuki Sugahara, Michael Amling, Petra Knaus, Danny Chan, Martin Lowe, Stefan Mundlos, Uwe Kornak
Gerodermia osteodysplastica (GO) is characterized by skin laxity and early-onset osteoporosis. GORAB, the responsible disease gene, encodes a small Golgi protein of poorly characterized function. To circumvent neonatal lethality of the GorabNull full knockout, Gorab was conditionally inactivated in mesenchymal progenitor cells (Prx1-cre), pre-osteoblasts (Runx2-cre), and late osteoblasts/osteocytes (Dmp1-cre), respectively. While in all three lines a reduction in trabecular bone density was evident, only GorabPrx1 and GorabRunx2 mutants showed dramatically thinned, porous cortical bone and spontaneous fractures...
March 21, 2018: PLoS Genetics
Siwei Chen, Ganming Deng, Kaiqun Li, Haonan Zheng, Gang Wang, Bin Yu, Kairui Zhang
BACKGROUND Previous studies demonstrated that tendon-derived stem cells (TDSCs) were vital healing cells and that mRNA expression of anti-inflammatory cytokine IL-6 was significantly upregulated in injured tendons. The aim of the present study was to investigate the effects of IL-6 on the TDSCs in vitro. MATERIAL AND METHODS TDSCs isolated from the Achilles tendons in SD rats were co-cultured with various concentrations of IL-6. Cell proliferation, cell cycle analysis, quantitative real-time PCR, western blotting analysis, and statistical analysis were used in the study...
March 16, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Brian A Aguado, Rachel M Hartfield, Grace G Bushnell, Joseph T Decker, Samira M Azarin, Dhaval Nanavati, Matthew J Schipma, Shreyas S Rao, Robert S Oakes, Yining Zhang, Jacqueline S Jeruss, Lonnie D Shea
Primary tumor (PT) immune cells and pre-metastatic niche (PMN) sites are critical to metastasis. Recently, synthetic biomaterial scaffolds used as PMN mimics are shown to capture both immune and metastatic tumor cells. Herein, studies are performed to investigate whether the scaffold-mediated redirection of immune and tumor cells would alter the primary tumor microenvironment (TME). Transcriptomic analysis of PT cells from scaffold-implanted and mock-surgery mice identifies differentially regulated pathways relevant to invasion and metastasis progression...
March 9, 2018: Advanced Healthcare Materials
Thomas N Wight
The content of proteoglycans (PGs) is low in the extracellular matrix (ECM) of vascular tissue, but increases dramatically in all phases of vascular disease. Early studies demonstrated that glycosaminoglycans (GAGs) including chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS) and heparan sulfate (HS) accumulate in vascular lesions in both humans and in animal models in areas of the vasculature that are susceptible to disease initiation (such as at branch points) and are frequently coincident with lipid deposits...
February 27, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Annele Orvokki Sainio, Hannu Tapio Järveläinen
Currently, the multifaceted role of the extracellular matrix (ECM) in tumorigenesis has been realized. One ECM macromolecule exhibiting potent oncosuppressive actions in tumorigenesis is decorin, the prototype of the small leucine-rich proteoglycan gene family. The actions of decorin include its capability to function as an endogenous pan-receptor tyrosine kinase inhibitor, a regulator of both autophagy and mitophagy, as well as a modulator of the immune system. In this review, we will discuss these topics in more detail...
February 27, 2018: British Journal of Pharmacology
Pedro Leme Silva, Fernanda Ferreira Cruz, Cynthia Dos Santos Samary, Lillian Moraes, Raquel Ferreira de Magalhães, Marcos Vinicius de S Fernandes, Rebeca Bose, Vitor B Pelegati, Hernandes F Carvalho, Vera Luiza Capelozzi, Joshua Satalin, Louis Gatto, Penny Andrews, Nader Habashi, Gary Nieman, Patricia R M Rocco
OBJECTIVES: To compare a time-controlled adaptive ventilation strategy, set in airway pressure release ventilation mode, versus a protective mechanical ventilation strategy in pulmonary and extrapulmonary acute respiratory distress syndrome with similar mechanical impairment. DESIGN: Animal study. SETTING: Laboratory investigation. SUBJECTS: Forty-two Wistar rats. INTERVENTIONS: Pulmonary acute respiratory distress syndrome and extrapulmonary acute respiratory distress syndrome were induced by instillation of Escherichia coli lipopolysaccharide intratracheally or intraperitoneally, respectively...
February 26, 2018: Critical Care Medicine
Mehmet Aral Atalay, Turan Ozmen, Bilge Cetinkaya Demir, Isil Kasapoglu, Guven Ozkaya
OBJECTIVE: To define serum decorin (sDEC) levels in healthy pregnants and in patients with preterm labor (PTL), and to introduce possible role of sDEC in predicting the risk for preterm birth (PTB). MATERIALS AND METHODS: Thirty-one women with diagnosis of PTL between 24th to 32nd weeks of pregnancy were compared with 44 healthy pregnants in this prospective case-control study. Maternal blood sDEC and uterine cervical length (CL) measurements were conducted at referral...
February 2018: Taiwanese Journal of Obstetrics & Gynecology
Marissa A Ruehle, Laxminarayanan Krishnan, Steven A LaBelle, Nick J Willett, Jeffrey A Weiss, Robert E Guldberg
Angiogenesis is a critical component during wound healing, and the process is sensitive to mechanical stimuli. Current in vitro culture environments used to investigate three-dimensional microvascular growth often lack dimensional stability and the ability to withstand compression. We investigated the ability of decorin, a proteoglycan known to modulate collagen fibrillogenesis, incorporated into a collagen hydrogel to increase construct dimensional stability while maintaining vascular growth. Decorin did not affect microvascular growth parameters, while increasing the compressive modulus of collagen gels and significantly reducing the contraction of 3% collagen gels after 16 days in culture...
September 2017: MRS Communications
Wen Zhang, Yan Ge, Qian Cheng, Qi Zhang, Lin Fang, Junnian Zheng
Decorin (DCN), an extracellular matrix (ECM) protein, belongs to the small leucine-rich proteoglycan family. As a pluripotent molecule, DCN regulates the bioactivities of cell growth factors and participates in ECM assembly. Accumulating evidence has shown that DCN acts as a ligand of various cytokines and growth factors by directly or indirectly interacting with the corresponding signalling molecules involved in cell growth, differentiation, proliferation, adhesion and metastasis and that DCN especially plays vital roles in cancer cell proliferation, spread, pro-inflammatory processes and anti-fibrillogenesis...
January 12, 2018: Oncotarget
W L O da Rosa, E Piva, A F Silva
The discovery that dentine is a reservoir of bioactive molecules that can be recruited on demand has attracted efforts to develop new protocols and materials for vital pulp therapy (VPT). The non-collagenous proteins (NCPs) present in the dentine extracellular matrix (ECM) include growth factors (TGF-β1, BMP-7, FGF-2, IGF-1 and -2, NGF, and GDNF), extracellular matrix molecules (DSP, DPP, BSP, DMP-1, and DSPP), and both anti- and pro-inflammatory chemokines and cytokines (TNF-α, IL-1, IL-6, and IL-10). Molecules such as DSP and DPP are mainly expressed by odontoblasts, and they are cleaved products from dentine sialophosphoprotein (DSPP)...
February 6, 2018: International Endodontic Journal
Patrick S Connell, Dragoslava P Vekilov, Christine M Diaz, Seulgi E Kim, K Jane Grande-Allen
Functional mitral regurgitation (FMR) is an insidious and poorly understood condition affecting patients with myocardial disease. While current treatments reduce regurgitation, their ability to reverse mitral valve pathology is unclear. We utilized a pseudo-physiological flow loop to study how repair impacted valve composition. Porcine mitral valves were cultured in control geometry (native papillary muscle position and annular area) or high-tension FMR geometry (5 mm apical and 5 mm lateral displacement of papillary muscles, 65% increased annular area) for 2 weeks...
February 5, 2018: Annals of Biomedical Engineering
Monica Montano, Kenneth H Dinnon, Logan Jacobs, William Xiang, Renato V Iozzo, Wade Bushman
BACKGROUND: Prostate ductal branching morphogenesis involves a complex spatiotemporal regulation of cellular proliferation and remodeling of the extracellular matrix (ECM) around the developing ducts. Decorin (Dcn) is a small leucine-rich proteoglycan known to sequester several growth factors and to act as a tumor suppressor in prostate cancer. RESULTS: Dcn expression in the developing prostate paralleled branching morphogenesis and was dynamically regulated by androgen and Hedgehog (Hh) signaling...
January 25, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
A T Jang, L Chen, A R Shimotake, W Landis, V Altoe, S Aloni, M Ryder, S P Ho
The load-bearing dentoalveolar fibrous joint is composed of biomechanically active periodontal ligament (PDL), bone, cementum, and the synergistic entheses of PDL-bone and PDL-cementum. Physiologic and pathologic loads on the dentoalveolar fibrous joint prompt natural shifts in strain gradients within mineralized and fibrous tissues and trigger a cascade of biochemical events within the widened and narrowed sites of the periodontal complex. This review highlights data from in situ biomechanical simulations that provide tooth movements relative to the alveolar socket...
March 2018: Journal of Dental Research
Selma Gogalic, Ursula Sauer, Sara Doppler, Claudia Preininger
A colorimetric microarray for the multiplexed detection of recurrence of bladder cancer including protein markers interleukin-8 (IL8), decorin (DCN), and vascular endothelial growth factor (VEGF) was established to enable easy and cheap read-out by a simple office scanner paving the way for quick therapy monitoring at doctors' offices. The chip is based on the principle of a sandwich immunoassay and was optimized prior to multiplexing using IL8 as a model marker. Six different colorimetric assay formats were evaluated using a detection antibody (dAB) labeled with (I) gold (Au) nanoparticles (NPs), (II) carbon NPs, (III) oxidized carbon NPs, and a biotinylated dAB in combination with (IV) neutravidin-carbon, (V) streptavidin (strp)-gold, and (VI) strp-horseradish peroxidase (HRP)...
January 24, 2018: Biosensors
Nicola Chiarelli, Giulia Carini, Nicoletta Zoppi, Marco Ritelli, Marina Colombi
Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures...
2018: PloS One
Janice A Vranka, Julia A Staverosky, Ashok P Reddy, Phillip A Wilmarth, Larry L David, Ted S Acott, Paul Russell, Vijay Krishna Raghunathan
Purpose: The extracellular matrix (ECM) of the trabecular meshwork (TM) modulates resistance to aqueous humor outflow, thereby regulating IOP. Glaucoma, a leading cause of irreversible blindness worldwide, is associated with changes in the ECM of the TM. The elastic modulus of glaucomatous TM is larger than age-matched normal TM; however, the biomechanical properties of segmental low (LF) and high flow (HF) TM regions and their response to elevated pressure, are unknown. Methods: We perfused human anterior segments at two pressures using an ex vivo organ culture system...
January 1, 2018: Investigative Ophthalmology & Visual Science
Svenja Hinderer, Katrin Sudrow, Maria Schneider, Monika Holeiter, Shannon Lee Layland, Martina Seifert, Katja Schenke-Layland
Decorin (DCN) is an important small leucine-rich proteoglycan present in the extracellular matrix (ECM) of many organs and tissues. Endothelial progenitor cells (EPCs) are able to interact with the surrounding ECM and bind to molecules such as DCN. Here, we recombinantly produced full-length human DCN under good laboratory practice (GLP) conditions, and after detailed immunological characterization, we investigated its potential to attract murine and human EPCs (mEPCs and hECFCs). Electrospun polymeric scaffolds were coated with DCN or stromal cell-derived factor-1 (SDF-1α) and were then dynamically cultured with both cell types...
January 8, 2018: Scientific Reports
David J Kirby, Marian F Young
Small leucine-rich proteoglycans (SLRPs) are a unique class of proteins that exist in the extracellular matrix, playing key roles in cell proliferation and function. In bone, SLRPs such as biglycan and decorin affect osteogenesis and bone remodeling. Their essential role in this organ system has created the need to isolate these proteins for study. Bone presents unique obstacles to the study of proteins; however, through the use of demineralizing agents, efficient methods of the purification of proteoglycans have been developed...
2018: Methods in Cell Biology
Amy K L Chui, Tilini N Gunatillake, Vera Ignjatovic, Paul T Monagle, Padma Murthi, Shaun P Brennecke, John M Whitelock, Joanne M Said
Pregnancies affected by preeclampsia (PE) or fetal growth restriction (FGR) display increases in thrombin generation and reductions in angiogenesis and cell growth. There is significant interest in the potential for low molecular weight heparins (LMWHs) to reduce the recurrence of PE and FGR. However, LMWH is associated with an increased risk of bleeding. Therefore, it is of vital importance to determine the exact molecular function of heparins in pregnancy if they are used as therapy for pregnant women. We aimed to determine this using our model for PE/FGR in microvascular endothelial cells...
July 11, 2017: Blood Advances
Madalina V Nastase, Andrea Janicova, Heiko Roedig, Louise Tzung-Harn Hsieh, Malgorzata Wygrecka, Liliana Schaefer
It is now well-established that members of the small leucine-rich proteoglycan (SLRP) family act in their soluble form, released proteolytically from the extracellular matrix (ECM), as danger-associated molecular patterns (DAMPs). By interacting with Toll-like receptors (TLRs) and the inflammasome, the two SLRPs, biglycan and decorin, autonomously trigger sterile inflammation. Recent data indicate that these SLRPs, besides their conventional role as pro-inflammatory DAMPs, additionally trigger anti-inflammatory signaling pathways to tightly control inflammation...
October 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
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