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Cartilage development

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https://www.readbyqxmd.com/read/28814230/virtual-screening-on-mmp-13-led-to-discovering-new-inhibitors-including-a-non-zinc-binding-and-a-micro-molar-one-a-successful-example-of-receptor-selection-according-to-cross-docking-results-for-a-flexible-enzyme
#1
Mohammad Ramezani, Jamal Shamsara
MMP-13 belongs to a large family of proteases called matrix metalloproteinases (MMPs) that degrades type II collagen, the main structural protein of articular cartilage. The main pathologic role of MMP-13 over expression is to contribute to the development of osteoarthritis. To find new inhibitors with possible selectivity for MMP-13 a structure based virtual screening was employed. The inhibitory activities of 11 inhibitors among 19 purchased compounds were approved by enzyme inhibition assay. Our results demonstrated that the CADD (computer aided drug design) could be successfully applied to find new MMP-13 inhibitors using a receptor structure (PDB code: 3O2X) which had been demonstrated a good performance in a cross-docking study...
August 16, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28812968/jnk-pathway-in-osteoarthritis-pathological-and-therapeutic-aspects
#2
Hong-Xing Ge, Fu-Man Zou, Yan Li, An-Min Liu, Min Tu
CONTEXT: Osteoarthritis (OA) is a common chronic degenerative joint disease resulting in physical disability and reduced quality of life. Different biochemical signaling pathways are involved in the progression of OA, including the c-Jun NH2-terminal kinase (JNK) signal transduction pathway. OBJECTIVE: In this study, we have reviewed the recent updates on the association of JNK pathway with OA. METHODS: In this review, we have explored the databases like PubMed, Google Scholar, Medline, Scopus, etc...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28812215/proteomic-alterations-associated-with-biomechanical-dysfunction-are-early-processes-in-the-emilin1-deficient-mouse-model-of-aortic-valve-disease
#3
P M Angel, D A Narmoneva, M K Sewell-Loftin, C Munjal, L Dupuis, B J Landis, A Jegga, C B Kern, W D Merryman, H S Baldwin, G M Bressan, Robert B Hinton
Aortic valve (AV) disease involves stiffening of the AV cusp with progression characterized by inflammation, fibrosis, and calcification. Here, we examine the relationship between biomechanical valve function and proteomic changes before and after the development of AV pathology in the Emilin1-/- mouse model of latent AV disease. Biomechanical studies were performed to quantify tissue stiffness at the macro (micropipette) and micro (atomic force microscopy (AFM)) levels. Micropipette studies showed that the Emilin1-/- AV annulus and cusp regions demonstrated increased stiffness only after the onset of AV disease...
August 15, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28810995/chondrocyte-viability-after-a-simulated-blast-exposure
#4
K Aaron Shaw, Peter C Johnson, David Williams, Steven D Zumbrun, Richard Topolski, Craig D Cameron
OBJECTIVES: The effects of blast exposure have gained increasing interest in the military medical community with their continued occurrence on the battlefield. The impact of the direct and indirect energy imparted from blasts to hollow viscera, as well as closed head injuries, have been well studied. However, the injury to articular cartilage has not been investigated, despite previous correlations regarding the development of osteoarthritis. The purpose of this study was to assess the degree of injury to articular chondrocytes after exposure to a simulated blast overpressure wave...
July 2017: Military Medicine
https://www.readbyqxmd.com/read/28810851/chitosan-in-viscosupplementation-in-vivo-effect-on-rabbit-subchondral-bone
#5
R Rieger, C Boulocher, S Kaderli, T Hoc
BACKGROUND: To investigate the effect of intra-articular injection of Chitosan (Cs) added to hyaluronic acid (HA) on subchondral bone during osteoarthritis (OA), microarchitectural parameters and mineral density were measured in a rabbit model of early OA. A novel hybrid hydrogel adding reacetylated Cs of fungal origin to HA was compared to high molecular weight HA commercial formulation. METHOD: Eighteen rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into three groups (Saline-group, HA-group and Hybrid-group) depending on the intra-articular injection compound...
August 15, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28808811/construction-and-biocompatibility-of-a-thin-type-i-ii-collagen-composite-scaffold
#6
Long Han, Zhong-Wen Zhang, Bo-He Wang, Zhen-Kun Wen
Articular cartilage injury is a common type of damage observed in clinical practice. A matrix-induced autologous chondrocyte implant was developed to repair articular cartilage as an advancement on the autologous chondrocyte implant procedure. Here, we establish a thin double layer of collagen as a novel and effective bioscaffold for the regeneration of cartilaginous lesions. We created a collagen membrane with double layers using a cover slip, a cover slip, and the collagen was then freeze-dried under vacuum...
August 14, 2017: Cell and Tissue Banking
https://www.readbyqxmd.com/read/28807995/regulation-of-the-cell-cycle-and-inflammatory-arthritis-by-the-transcription-cofactor-lbh-gene
#7
Shinji Matsuda, Deepa Hammaker, Katharyn Topolewski, Karoline J Briegel, David L Boyle, Steven Dowdy, Wei Wang, Gary S Firestein
Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) display unique aggressive behavior, invading the articular cartilage and promoting inflammation. Using an integrative analysis of RA risk alleles, the transcriptome and methylome in RA FLS, we recently identified the limb bud and heart development (LBH) gene as a key dysregulated gene in RA and other autoimmune diseases. Although some evidence suggests that LBH could modulate the cell cycle, the precise mechanism is unknown and its impact on inflammation in vivo has not been defined...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28807034/exosomes-from-embryonic-mesenchymal-stem-cells-alleviate-osteoarthritis-through-balancing-synthesis-and-degradation-of-cartilage-extracellular-matrix
#8
Yafei Wang, Dongsheng Yu, Zhiming Liu, Fang Zhou, Jun Dai, Bingbing Wu, Jing Zhou, Boon Chin Heng, Xiao Hui Zou, Hongwei Ouyang, Hua Liu
BACKGROUND: Mesenchymal stem cell therapy for osteoarthritis (OA) has been widely investigated, but the mechanisms are still unclear. Exosomes that serve as carriers of genetic information have been implicated in many diseases and are known to participate in many physiological processes. Here, we investigate the therapeutic potential of exosomes from human embryonic stem cell-induced mesenchymal stem cells (ESC-MSCs) in alleviating osteoarthritis (OA). METHODS: Exosomes were harvested from conditioned culture media of ESC-MSCs by a sequential centrifugation process...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28806096/results-of-anterior-cruciate-ligament-reconstruction-with-patellar-tendon-autografts-objective-factors-associated-with-the-development-of-osteoarthritis-at-20-to-33-years-after-surgery
#9
K Donald Shelbourne, Rodney W Benner, Tinker Gray
BACKGROUND: Few studies exist that report objective radiographic and physical examination results at >20 years after anterior cruciate ligament (ACL) reconstruction. HYPOTHESIS: The risk of osteoarthritis (OA) at >20 years after surgery would be statistically significantly higher if an increased severity of factors was present. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Between 1982 and 1994, 1428 knees met the inclusion criteria of being primary ACL surgery, having no existing OA or other ligamentous laxity, and having no known graft tear...
August 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28801212/intraoperative-validation-of-quantitative-t2-mapping-in-patients-with-articular-cartilage-lesions-of-the-knee
#10
Stefan Soellner, Axel Goldmann, Daniel Muelheims, Goetz H Welsch, Milena Pachowsky
OBJECTIVE: The aim of this study was to compare T2 relaxation times of knee cartilage with intraoperative results for the assessment of early osteoarthritis (OA) and to define T2 values for the differentiation between healthy and degenerated cartilage. DESIGN: Twenty-one patients with cartilage lesions or moderate OA were examined using 3T MRI. In this prospective study, a total of 882 regions of interest (ROIs) were examined by a sagittal, multi-echo, spin-echo T2 sequence and a morphological high-resolution three-dimensional, fat-saturated proton-density space sequence...
August 8, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28801211/parkin-clearance-of-dysfunctional-mitochondria-regulates-ros-levels-and-increases-survival-of-human-chondrocytes
#11
Mohammad Y Ansari, Nazir M Khan, Imran Ahmad, Tariq M Haqqi
OBJECTIVE: Mitochondrial dysfunction, oxidative stress and chondrocyte death are important contributors to the development and pathogenesis of osteoarthritis (OA). In this study, we determined the expression and role of Parkin in the clearance of damaged/dysfunctional mitochondria, regulation of reactive oxygen species (ROS) levels and chondrocyte survival under pathological conditions. METHODS: Human chondrocytes were from the unaffected area of knee OA cartilage (n = 12) and were stimulated with IL-1β to mimic pathological conditions...
August 8, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28800889/spatio-temporal-expression-patterns-of-wnt-signaling-pathway-during-the-development-of-temporomandibular-condylar-cartilage
#12
Kan Chen, Huixin Quan, Gang Chen, Di Xiao
There is a growing body of evidence supporting the involvement of the Wnt signaling pathway in various aspects of skeletal and joint development; however, it is unclear whether it is involved in the process of temporomandibular joint development. In order to clarify this issue, we examined the spatio-temporal distribution of mRNAs and proteins of the Wnt family during the formation of the mandibular condylar cartilage at the prenatal and postnatal stages. An in situ hybridization test revealed no mRNAs of β-catenin and Axin2 during early mesenchymal condensation; the ligands surveyed in this study (including Wnt-4, 5a, and 9a) were clearly detected at various ranges of expression, mainly in the condylar blastema and later distinct cartilaginous layers...
August 8, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28800252/progressive-changes-in-walking-kinematics-and-kinetics-after-anterior-cruciate-ligament-injury-and-reconstruction-a-review-and-meta-analysis
#13
Lindsay V Slater, Joseph M Hart, Adam R Kelly, Christopher M Kuenze
CONTEXT:   Anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR) result in persistent alterations in lower extremity movement patterns. The progression of lower extremity biomechanics from the time of injury has not been described. OBJECTIVE:   To compare the 3-dimensional (3D) lower extremity kinematics and kinetics of walking among individuals with ACL deficiency (ACLD), individuals with ACLR, and healthy control participants from 3 to 64 months after ACLR...
August 11, 2017: Journal of Athletic Training
https://www.readbyqxmd.com/read/28798204/imaging-igf-i-uptake-in-growth-plate-cartilage-using-in-vivo-multiphoton-microscopy
#14
Maria A Serrat, Gabriela Ion
Bones elongate through endochondral ossification in cartilaginous growth plates located at ends of primary long bones. Linear growth ensues from a cascade of biochemical signals initiated by actions of systemic and local regulators on growth plate chondrocytes. Although cellular processes are well defined, there is a fundamental gap in understanding how growth regulators are physically transported from surrounding blood vessels into and through dense, avascular cartilage matrix. Intravital imaging using in vivo multiphoton microscopy is one promising strategy to overcome this barrier by quantitatively tracking molecular delivery to cartilage from the vasculature in real time...
August 10, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28798097/suramin-inhibits-osteoarthritic-cartilage-degradation-by-increasing-extracellular-levels-of-chondroprotective-tissue-inhibitor-of-metalloproteinases-3-timp-3
#15
Anastasios Chanalaris, Christine Doherty, Brian D Marsden, Gabriel Bambridge, Stephen P Wren, Hideaki Nagase, Linda Troeberg
Osteoarthritis is a common degenerative joint disease for which no disease-modifying drugs are currently available. Attempts to treat the disease with small molecule inhibitors of the metalloproteinases that degrade the cartilage matrix have been hampered by a lack of specificity. We aimed to inhibit cartilage degradation by augmenting levels of the endogenous metalloproteinase inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP-3), through blocking its interaction with the endocytic scavenger receptor, low-density lipoprotein receptor-related protein 1 (LRP1)...
August 10, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28793886/cathepsin-s-degraded-decorin-are-elevated-in-fibrotic-lung-disorders-development-and-biological-validation-of-a-new-serum-biomarker
#16
S N Kehlet, C L Bager, N Willumsen, B Dasgupta, C Brodmerkel, M Curran, S Brix, D J Leeming, M A Karsdal
BACKGROUND: Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue homeostasis contributing to extracellular matrix remodeling diseases. Here, we present the development and validation of a competitive enzyme-linked immunosorbent assay (ELISA) quantifying a specific fragment of degraded decorin, which has potential as a novel non-invasive serum biomarker for fibrotic lung disorders...
August 9, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28790486/the-role-of-aging-in-the-development-of-osteoarthritis
#17
Richard F Loeser
Osteoarthritis (OA) is the most common form of arthritis and a significant cause of pain and disability in older adults. Among the risk factors for OA, age is the most prominent. This review will discuss the relationship between aging and the development of OA, with a particular focus on mechanisms relevant to cartilage degeneration and the role of excessive levels of reactive oxygen species. Rather than just causing random oxidative damage, an increase in reactive oxygen species that leads to oxidative stress disrupts specific cell signaling pathways...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28783116/teratogenic-effects-of-topiramate-in-a-zebrafish-model
#18
Yu-Heng Lai, Yu-Ju Ding, David Moses, Yau-Hung Chen
Topiramate is commonly used for treating epilepsy in both children and adults. Recent clinical data suggests that administration of topiramate to women during pregnancy increases the risk of oral clefts in their offspring. To better understand the potential effects of topiramate, we dosed adult female zebrafish with topiramate, and investigated the altered morphologies in adult females and their offspring. It showed that topiramate-treated female fish had reduced oocyte maturation, and the survival rates of their offspring were seriously decreased during embryogenesis...
August 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28782721/engineering-cell-aggregates-through-incorporated-polymeric-microparticles
#19
REVIEW
Caroline C Ahrens, Ziye Dong, Wei Li
Ex vivo cell aggregates must overcome significant limitations in the transport of nutrients, drugs, and signaling proteins compared to vascularized native tissue. Further, engineered extracellular environments often fail to sufficiently replicate tethered signaling cues and the complex architecture of native tissue. Co-cultures of cells with microparticles (MPs) is a growing field directed towards overcoming many of these challenges by providing local and controlled presentation of both soluble and tethered proteins and small molecules...
August 4, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28782699/does-curettage-cement-packing-for-treating-giant-cell-tumors-at-the-knee-lead-to-osteoarthritis
#20
A Caubère, S Harrosch, M Fioravanti, G Curvale, A Rochwerger, J C Mattei
INTRODUCTION: Giant cell tumors (GCTs) make up 15% to 20% of bone-related tumors in adults. They are often found around the knee in the metaphysis and epiphysis area, contacting the joint cartilage. The aims of our study were to evaluate the presence of early knee osteoarthritis (OA) in patients with GCTs in the knee area treated by curettage-cement packing, and to evaluate whether replacing subchondral bone with acrylic cement has an effect on the functional outcomes and quality of life...
August 3, 2017: Orthopaedics & Traumatology, Surgery & Research: OTSR
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