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Satyavrata Samavedi, Patricia Diaz-Rodriguez, Joshua Dean Erndt-Marino, Mariah Hahn
The goal of the present study was to develop a fully 3D co-culture system that would allow for systematic investigation of the interplay between activated macrophages and chondrocytes in osteoarthritic disease progression. Toward this end, our 3D co-culture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs) ─ in 2D or 3D ─ with 2D classically activated macrophages (AMs). In the current work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to better mimic the native 3D environments of both cell types within the osteoarthritic joint...
October 13, 2016: Tissue Engineering. Part A
Carlo R Bartoli, Jooeun Kang, David Zhang, Jessica Howard, Michael Acker, Pavan Atluri, Tadashi Motomura
BACKGROUND: Supraphysiologic shear stress from continuous-flow left ventricular assist devices (LVADs) accelerates von Willebrand factor (vWF) degradation and predisposes patients to nonsurgical bleeding. It is unknown whether unique design characteristics of LVADs differentially affect vWF degradation. We tested the hypothesis that the centrifugal-flow EVAHEART (Evaheart, Houston, TX) left ventricular assist system (LVAS), which was designed to minimize shear stress (low operational revolutions per minute [rpm], larger flow gaps, low shear stress, flat H-Q curve), reduced vWF degradation versus the axial-flow HeartMate II (Thoratec, Pleasanton, CA) LVAD...
October 4, 2016: Annals of Thoracic Surgery
Ann Ouyang, Alec E Cerchiari, Xinyan Tang, Ellen Liebenberg, Tamara Alliston, Zev J Gartner, Jeffrey C Lotz
Tissue engineering constructs to treat intervertebral disc degeneration must adapt to the hypoxic and inflammatory degenerative disc microenvironment. The objective of this study was to determine the effects of two key design factors, cell type and cell configuration, on the regenerative potential of nucleus pulposus cell (NPC) and mesenchymal stem cell (MSC) constructs. Anabolic and catabolic activity was quantified in constructs of varying cell type (NPCs, MSCs, and a 50:50 coculture) and varying configuration (individual cells and micropellets)...
October 4, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Weiwei Lu, Jia Shi, Jinming Zhang, Zhengtao Lv, Fengjing Guo, Hui Huang, Wentao Zhu, Anmin Chen
We evaluated the role of the CXCL12/CXCR4 (C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4) axis in aggrecanase-mediated cartilage degradation, and explored the underlying mechanism in a post-traumatic osteoarthritis rat model. Expression of CXCL12/CXCR4 and ADAMTS-5 was analyzed in the knees of osteoarthritic and non-arthritic rats using Western blot, ELISA, immunohistochemistry and immunofluorescence. Rodent studies were performed using Sprague-Dawley rats, with animals divided into three groups: Destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), DMM/PBS-treated, and sham controls...
2016: International Journal of Molecular Sciences
Lijing Liu, Hong Qian, Hua Xiao, Jianbin He, Maofeng Xie, Zaiyan Wang, Xingyun Long
Objective To explore the role of transforming growth factor-β1 (TGF-β1)/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) signaling pathway in emodin's anti-pulmonary fibrosis. Methods Sixty SD rats were randomly divided into 6 groups: normal control group, sham-operated group, model group, low-dose emodin intervention group (20 mg/kg), high-dose emodin intervention group (80 mg/kg) and prednisone group (5 mg/kg). Each group included 10 animals. Rats in the latter 4 groups were intratracheally injected with bleomycin A5 to induce pulmonary fibrosis, whereas bleomycin A5 was replaced by normal saline in sham-operated group...
October 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
R K Tilwani, S Vessillier, B Pingguan-Murphy, D A Lee, D L Bader, T T Chowdhury
OBJECTIVE AND DESIGN: Oxygen tension and biomechanical signals are factors that regulate inflammatory mechanisms in chondrocytes. We examined whether low oxygen tension influenced the cells response to TNFα and dynamic compression. MATERIALS AND METHODS: Chondrocyte/agarose constructs were treated with varying concentrations of TNFα (0.1-100 ng/ml) and cultured at 5 and 21 % oxygen tension for 48 h. In separate experiments, constructs were subjected to dynamic compression (15 %) and treated with TNFα (10 ng/ml) and/or L-NIO (1 mM) at 5 and 21 % oxygen tension using an ex vivo bioreactor for 48 h...
September 22, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Ting Xu, Gaoli Xu, Zhiyuan Gu, Huiling Wu
OBJECTIVE: The aim of this study was to investigate the changes in hedgehog (Hh) expression and its possible effects on cartilage degeneration in adjuvant-induced temporomandibular joint osteoarthritis (TMJOA) of rats. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into experimental osteoarthritis (OA) and sham control groups. The bilateral TMJs of six rats from each group were harvested at three, seven, 14, and 28 days. Histological changes in condylar cartilage were assessed by hematoxylin and eosin, toluidine blue, and safranin O staining...
September 20, 2016: Journal of Oral Pathology & Medicine
Dalya Ataca, Marian Caikovski, Alessandra Piersigilli, Alexandre Moulin, Charaf Benarafa, Sarah E Earp, Yakir Guri, Corinne Kostic, Yvan Arsenivic, Raija Soininen, Suneel S Apte, Cathrin Brisken
The ADAMTS family comprises 19 secreted metalloproteinases that cleave extracellular matrix components and have diverse functions in numerous disease and physiological contexts. A number of them remain 'orphan' proteases, among them ADAMTS18, which has been implicated in developmental eye disorders, platelet function and various malignancies. To assess in vivo function of ADAMTS18, we generated a mouse strain with inactivated Adamts18 alleles. In the C57Bl6/Ola background, Adamts18 deficient mice are born in a normal Mendelian ratio, and are viable but show a transient growth delay...
October 11, 2016: Biology Open
Daniel C Moreira, Christopher J Ng, Ralph Quinones, Xiayuan Liang, Dominic W Chung, Jorge Di Paola
Idiopathic systemic capillary leak syndrome (SCLS) is a rare process characterized by acute and recurrent episodes of vascular leakage with severe hypotension, hypoalbuminemia, hemoconcentration and edema. Anemia and thrombocytopenia are not part of this syndrome, but here we present the case of a pediatric patient with a clinical presentation consistent with SCLS who subsequently developed microangiopathic hemolytic anemia at a time when she had significant fluid loss and anasarca. Based on serial ADAMTS-13 levels, we propose that the anemia in this patent developed as a result of ADAMTS-13 loss in the third-space fluid, a novel mechanism for acquired microangiopathic hemolytic anemia...
September 13, 2016: Journal of Thrombosis and Haemostasis: JTH
Joseph Rosenthal
Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. Thrombotic microangiopathy may affect multiple systems and occurs in ~30% of patients undergoing hematopoietic stem cell transplantation. A subgroup of patients with thrombotic microangiopathy develop TA-TMA, and the other may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura, a condition with similar finding but different pathophysiology involving ADAMTS-13...
2016: Journal of Blood Medicine
Emily Fuller, Christopher B Little, James Melrose
We have developed an ovine meniscal explant model where the focal degradative events leading to characteristic fragmentation patterns of biglycan in human OA of the knee and hip, and evident in animal models of knee OA and IVD degeneration are reproduced in culture. Lateral and medial menisci were dissected into outer, mid and inner zones and established in explant culture±IL-1 (10ng/ml). The biglycan species present in conditioned media samples and in GuHCl extracts of tissues were examined by Western blotting using two C-terminal antibodies PR-85 and EF-Bgn...
September 9, 2016: Experimental and Molecular Pathology
Anwar Al-Awadhi, Adekunle Adekile, Rajaa Marouf
Sickle cell disease (SCD) is a severe form of hemolytic anemia characterized by chronic hemolysis and is associated with increased thrombotic risk. Elevated von Willebrand factor (vWF) levels in SCD have been attributed to increased secretion and impaired processing by its cleaving protease ADAMTS-13. In this study we measured vWF and ADAMTS-13 antigen and activity levels in our SCD patients. Hematological and biochemical parameters for 59 SCD patients (20 children and 39 adults) were analyzed and compared to 59 age- and sex-matched controls...
September 9, 2016: Journal of Thrombosis and Thrombolysis
Kang Xu, Xiaofei Wang, Qianshi Zhang, Anjing Liang, Haipeng Zhu, Dongsheng Huang, Chunhai Li, Wei Ye
During the pathogenesis of intervertebral disc degeneration, pro‑inflammatory cytokines, including tumor necrosis factor‑α (TNF‑α), stimulate the degradation of the extracellular matrix (ECM) of intervertebral discs via the activity of catabolic enzymes including matrix metalloproteinases (MMPs), disintegrins and metalloproteinases with thrombospondin motifs (ADAMTSs), and cyclooxygenase 2 (Cox2). The transcriptional promoters of the human catabolic enzymes MMPs, ADAMTS, Cox2 and Syndecan 4 contain at least one specificity protein‑1 (Sp1) transcription factor‑binding site...
October 2016: Molecular Medicine Reports
Pei Li, Yibo Gan, Yuan Xu, Lei Song, Haoming Wang, Chengmin Zhang, Liyuan Wang, Chen Zhao, Lei Luo, Qiang Zhou
Evidence suggests that mechanical load is related to structural destruction of disk annulus fibrosus (AF) either in adult disk degeneration or in child disk acute injury. Both biochemical and biomechanical properties are different between immature and mature disks. However, the effects of mechanical compression on immature AF are not fully clear. This study was to investigate the effects of a relatively wide range of dynamic compressive frequency on matrix homeostasis within the immature AF. Immature disks from pig (3-4 months) were randomly assigned into the control group (non-compression) and compression groups (0...
September 2, 2016: Biomechanics and Modeling in Mechanobiology
Christine M Doherty, Robert Visse, Deendayal Dinakarpandian, Dudley K Strickland, Hideaki Nagase, Linda Troeberg
Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a central inhibitor of matrix-degrading and sheddase families of metalloproteinases. Extracellular levels of the inhibitor are regulated by the balance between its retention on the extracellular matrix and its endocytic clearance by the scavenger receptor low density lipoprotein receptor-related protein 1 (LRP1). Here, we used molecular modeling to predict TIMP-3 residues potentially involved in binding to LRP1 based on the proposed LRP1 binding motif of 2 lysine residues separated by about 21 Å and mutated the candidate lysine residues to alanine individually and in pairs...
October 14, 2016: Journal of Biological Chemistry
Shuang Zheng, David J Hunter, Jianhua Xu, Changhai Ding
INTRODUCTION: Osteoarthritis (OA) is a multifactorial chronic joint disease, and so far, there are no approved disease-modifying anti-OA drugs (DMOADs). There is an urgent need to develop therapies for different phenotypes of OA. Monoclonal antibodies (mAb) may slow structural progression, control inflammation and relieve pain, and thus have the potential to be DMOADs. AREAS COVERED: In this review, the authors searched the literature on PubMed, EMBASE and the Cochrane Library using keywords, including mAbs, biological agents, OA and osteoarthritis, electronically up to May 2016...
September 11, 2016: Expert Opinion on Biological Therapy
M A H Sonneveld, M Kavousi, M A Ikram, A Hofman, O L Rueda Ochoa, P L Turecek, O H Franco, F W G Leebeek, M P M de Maat
: Essentials An association between ADAMTS-13 and coronary heart disease (CHD) has been suggested. 5688 participants ≥ 55 years from the Rotterdam Study without a history of CHD were included. Over a median follow-up time of 9.7 years, 456 individuals suffered from CHD. Low ADAMTS-13 activity was associated with an increased CHD risk. SUMMARY: Background The metalloprotease ADAMTS-13 cleaves high-molecular-weight von Willebrand factor multimers into smaller, less procoagulant forms...
August 25, 2016: Journal of Thrombosis and Haemostasis: JTH
Raffaella Cravero, Gianluigi Ardissino, Umberto Colageo, Piernicola Staffa, Elena Bruschetta, Serena Maroni, Eirini Karvela, Ermanno Spagarino, Velia Ruggeri, Roberto Jura
Pregnancy-associated thrombotic microangiopathy (TMA) is a rare condition, but it is burdened by a significant perinatal and maternal morbidity as well as mortality. We describe the case of a 33-year-old woman, who developed a TMA at the 36th week of gestation characterized by increased LDH, haptoglobin consumption, schistocytes, thrombocytopenia and acute renal failure requiring dialysis. There were not gestational hypertension nor proteinuria until the day of hospitalization. ADAMTS 13 deficiency was ruled out and the patient did not have diarrhea...
July 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Yuxin Xie, Qiheng Gou, Keqi Xie, Zhu Wang, Yanping Wang, Hong Zheng
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is involved in tumor development. However, how ADAMTS6 influences cancer remains unknown. We investigated the biological function and clinical implications of ADAMTs6 in breast cancer (BC). Its functional significance in BC cell lines was confirmed by ADAMTs6 overexpression or downregulation both in vitro and in vivo studies. Enhanced ADAMTS6 expression suppressed cell migration, invasion, and tumorigenesis, whereas knockdown promoted these characteristics...
August 17, 2016: Oncotarget
Linwei Chen, Yaosen Wu, Yan Wu, Ye Wang, Liaojun Sun, Fangcai Li
The purpose of our study was to elucidate the role of the histone methyltransferase enhancer of zeste homologue 2 (EZH2) in the pathophysiology of osteoarthritis (OA) and to develop a strategy to modulate EZH2 activity for OA treatment. The expression of EZH2 in normal and OA human cartilage was compared by western blotting. The effect of EZH2 overexpression and inhibition on chondrocyte hypertrophy related gene expression was examined by real-time PCR, and histone methylation on the promoter of the Wnt inhibitor SFRP1 was analyzed using a chromatin immunoprecipitation (ChIP) PCR...
2016: Scientific Reports
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