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https://www.readbyqxmd.com/read/28604608/friction-induced-mitochondrial-dysregulation-contributes-to-joint-deterioration-in-prg4-knockout-mice
#1
Kimberly A Waller, Ling X Zhang, Gregory D Jay
Deficiency of PRG4 (lubricin), the boundary lubricant in mammalian joints, contributes to increased joint friction accompanied by superficial and upper intermediate zone chondrocyte caspase-3 activation, as shown in lubricin-null (Prg4(-/-)) mice. Caspase-3 activity appears to be reversible upon the restitution of Prg4 either endogenously in vivo, in a gene trap mouse, or as an applied lubricant in vitro. In this study we show that intra-articular injection of human PRG4 in vivo in Prg4(-/-) mice prevented caspase-3 activation in superficial zone chondrocytes and was associated with a modest decrease in whole joint friction measured ex vivo using a joint pendulum method...
June 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28579418/early-genetic-restoration-of-lubricin-expression-in-transgenic-mice-mitigates-chondrocyte-peroxynitrite-release-and-caspase-3-activation
#2
K M Larson, L Zhang, G J Badger, G D Jay
OBJECTIVE: This study investigated the ability of endogenous lubricin secretion to restore joint health following a brief <21 day, postnatal lubricin-null state, in a C57BL/6J Prg4 gene trap (GT) mouse under the control of cre-recombinase. Previously we showed that re-expression of lubricin at 21 days was partly restorative of joint lubrication. DESIGN: The tibio-femoral joints of adult C57BL/6J mice containing lubricin, lacking lubricin, and postnatally lacking lubricin until restoration of lubricin expression at 7 days or 14 days of age were evaluated ex vivo...
June 1, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28578597/optimization-of-methods-for-articular-cartilage-surface-tissue-engineering-cell-density-and-tgf-b-are-critical-self-assembly-and-lubricin-secretion
#3
Kenjiro Iwasa, A Hari Reddi
Objective; Lubricin/Superficial zone protein (SZP)/PRG4 plays an important role in boundary lubrication in articular cartilage. Lubricin is secreted by superficial zone chondrocytes. The specific objective of this investigation is to optimize the methods for tissue engineering of articular cartilage surface. The aim of this study is to investigate the effect of cell density on the self-assembly of superficial zone chondrocytes and attendant lubricin secretion as a functional assessment. Design; Superficial zone chondrocytes were cultivated as a monolayer at low, medium and high densities...
June 3, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28549901/degradation-of-proteoglycan-4-lubricin-by-cathepsin-s-potential-mechanism-for-diminished-ocular-surface-lubrication-in-sj%C3%A3-gren-s-syndrome
#4
Suresh C Regmi, Michael L Samsom, Miriam L Heynen, Gregory D Jay, Benjamin D Sullivan, Sruthi Srinivasan, Barbara Caffery, Lyndon Jones, Tannin A Schmidt
Sjögren's syndrome (SS) is an autoimmune disease affecting the lacrimal and salivary glands with hallmark clinical symptoms of dry eye and dry mouth. Recently, markedly increased cathepsin S (CTSS) activity has been observed in the tears of SS patients. Proteoglycan 4 (PRG4), also known as lubricin, is an effective boundary lubricant that is naturally present on the ocular surface. While PRG4 is susceptible to proteolytic digestion, the potential effect of CTSS on PRG4 remains unknown. The objective of this study was to assess the ability of CTSS to enzymatically degrade purified PRG4, and PRG4 naturally present in human tears, and alter ocular surface boundary lubricating properties...
May 23, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28529106/engineered-cartilage-regeneration-from-adipose-tissue-derived-mesenchymal-stem-cells-a-morphomolecular-study-on-osteoblast-chondrocyte-and-apoptosis-evaluation
#5
Marta Anna Szychlinska, Paola Castrogiovanni, Houda Nsir, Michelino Di Rosa, Claudia Guglielmino, Rosalba Parenti, Giovanna Calabrese, Elisabetta Pricoco, Lucia Salvatorelli, Gaetano Magro, Rosa Imbesi, Ali Mobasheri, Giuseppe Musumeci
The poor self-repair capacity of cartilage tissue in degenerative conditions, such as osteoarthritis (OA), has prompted the development of a variety of therapeutic approaches, such as cellular therapies and tissue engineering based on the use of mesenchymal stem cells (MSCs). The aim of this study is to demonstrate, for the first time, that the chondrocytes differentiated from rat adipose tissue derived-MSCs (AMSCs), are able to constitute a morphologically and biochemically healthy hyaline cartilage after 6 weeks of culture on a Collagen Cell Carrier (CCC) scaffold...
May 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28525322/a-systemic-review-of-existing-serological-possibilities-to-diagnose-canine-osteoarthritis-with-a-particular-focus-on-extracellular-matrix-proteoglycans-and-protein
#6
M Shahid, G Manchi, P Slunsky, O Naseer, A Fatima, B Leo, J Raila
Extra-cellular matrix (ECM) components are important and their stabilization is significant in maintaining normal healthy joint environment. In osteoarthritis (OA), ECM components are altered and indicate disease progression. The joint ECM is composed of proteoglycans (aggrecan, perlecan, inter α-trypsin inhibitor), glycoproteins (fibronectin, lubricin, COMP) and collagen types (most abundantly collagen type II) which represent structural and functional transformation during disease advancement. ECM investigation revealed significant biomarkers of OA that could be used as a diagnostic and therapeutic tool in different canine orthopedic diseases...
March 28, 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28482921/the-autocrine-role-of-proteoglycan-4-prg4-in-modulating-osteoarthritic-synoviocyte-proliferation-and-expression-of-matrix-degrading-enzymes
#7
Ali Alquraini, Maha Jamal, Ling Zhang, Tannin Schmidt, Gregory D Jay, Khaled A Elsaid
BACKGROUND: Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation. The objective of this study is to decipher the autocrine function of PRG4 in regulating osteoarthritic synoviocyte proliferation and expression of catabolic and pro-inflammatory mediators under basal and interleukin-1 beta (IL-1β)-stimulated conditions...
May 8, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28474537/physioxia-promotes-the-articular-chondrocyte-like-phenotype-in-human-chondroprogenitor-derived-self-organized-tissue
#8
Devon E Anderson, Brandon Markway, Kenneth J Weekes, Helen E McCarthy, Brian Johnstone
INTRODUCTION: Biomaterial-based tissue engineering has not successfully reproduced the structural architecture or functional mechanical properties of native articular cartilage. In scaffold-free tissue engineering systems, cells secrete and organize the entire extracellular matrix over time in response to environmental signals, such as oxygen level. In this study, we investigated the effect of oxygen on the formation of neocartilage from human-derived chondrogenic cells. METHODS: Articular chondrocytes (ACs) and articular cartilage progenitor cells (ACPs) derived from healthy human adults were guided toward cell condensation by centrifugation onto plate inserts that were uncoated or coated with either agarose or fibronectin...
May 5, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28469288/friction-properties-of-a-new-silk-fibroin-scaffold-for-meniscal-replacement
#9
Daniela Warnecke, N B Schild, S Klose, H Joos, R E Brenner, O Kessler, N Skaer, R Walker, M Freutel, A Ignatius, L Dürselen
The menisci protect the articular cartilage by reducing contact pressure in the knee. To restore their function after injury, a new silk fibroin replacement scaffold was developed. To elucidate its tribological properties, friction of the implant was tested against cartilage and glass, where the latter is typically used in tribological cartilage studies. The silk scaffold exhibited a friction coefficient against cartilage of 0.056, which is higher than meniscus against cartilage but in range of the requirements for meniscal replacements...
May 2017: Tribology International
https://www.readbyqxmd.com/read/28373131/cartilage-oligomeric-matrix-protein-forms-protein-complexes-with-synovial-lubricin-via-non-covalent-and-covalent-interactions
#10
S A Flowers, S Kalamajski, L Ali, L I Björkman, J R Raj, A Aspberg, N G Karlsson, C Jin
OBJECTIVE: Understanding the cartilage surface structure, lost in arthritic disease, is essential for developing strategies to effectively restore it. Given that adherence of the lubricating protein, lubricin, to the cartilage surface is critical for boundary lubrication, an interaction with cartilage oligomeric matrix protein (COMP) was investigated. COMP, an abundant cartilage protein, is known to be important for matrix formation. DESIGN: Synovial fluid (SF) from arthritic patients was used to detect possible COMP-lubricin complexes by immunological methods...
April 1, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28266618/confocal-imaging-of-mouse-mandibular-condyle-cartilage
#11
Y He, M Zhang, A Y Huang, Y Cui, D Bai, M L Warman
Mice are commonly used to study the temporomandibular joint (TMJ) and to model human TMJ disease. However, evaluating TMJ pathology in mice using standard histologic methods is time consuming, labor intensive, and dependent upon investigators' expertise at consistently orienting and sectioning across tiny specimens. We describe a method that uses confocal microscopy to rapidly and reliably assess indicators of mandibular condyle cartilage pathology in mice. We demonstrate the utility of this method for detecting abnormalities in chondrocyte distribution in mice lacking lubricin (Prg4), the major boundary lubricant of articular cartilage...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28215089/structure-and-property-changes-in-self-assembled-lubricin-layers-induced-by-calcium-ion-interactions
#12
George W Greene, Rajiv Thapa, Stephen A Holt, Xiaoen Wang, Christopher J Garvey, Rico F Tabor
Lubricin (LUB) is a "mucin-like" glycoprotein found in synovial fluids and coating the cartilage surfaces of articular joints, which is now generally accepted as one of the body's primary boundary lubricants and antiadhesive agents. LUB's superior lubrication and antiadhesion are believed to derive from its unique interfacial properties by which LUB molecules adhere to surfaces (and biomolecules, such as hyaluronic acid and collagen) through discrete interactions localized to its two terminal end domains. These regionally specific interactions lead to self-assembly behavior and the formation of a well-ordered "telechelic" polymer brush structure on most substrates...
March 14, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28208081/molecular-synergy-in-biolubrication-the-role-of-cartilage-oligomeric-matrix-protein-comp-in-surface-structuring-of-lubricin
#13
Akanksha Raj, Min Wang, Chao Liu, Liaquat Ali, Niclas G Karlsson, Per M Claesson, Andra Dėdinaitė
HYPOTHESIS: Synovial surfaces are lubricated by biomolecular aggregates that act in synergy, and lubricin is one key biolubricant. Its molecular structure allows extensive hydration and this is conducive to its lubrication performance. However, in order to fullfil its lubrication function it needs to be anchored and oriented on the surface in a proper way. We suggest that cartilage oligomeric matrix protein (COMP) is one of the biomolecules that promotes anchoring of lubricin in a fashion that facilitates lubrication...
June 1, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28169453/mechanical-properties-and-structure-function-relationships-of-human-chondrocyte-seeded-cartilage-constructs-after-in-vitro-culture
#14
Jill M Middendorf, Darvin J Griffin, Sonya Shortkroff, Caroline Dugopolski, Stephen Kennedy, Joseph Siemiatkoski, Itai Cohen, Lawrence J Bonassar
Autologous Chondrocyte Implantation (ACI) is a widely recognized method for the repair of focal cartilage defects. Despite the accepted use, problems with this technique still exist, including graft hypertrophy, damage to surrounding tissue by sutures, uneven cell distribution, and delamination. Modified ACI techniques overcome these challenges by seeding autologous chondrocytes onto a 3D scaffold and securing the graft into the defect. Many studies on these tissue engineered grafts have identified the compressive properties, but few have examined frictional and shear properties as suggested by FDA guidance...
February 7, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28129516/intra-articular-recombinant-human-proteoglycan-4-mitigates-cartilage-damage-after-destabilization-of-the-medial-meniscus-in-the-yucatan-minipig
#15
Kimberly A Waller, Kaitlyn E Chin, Gregory D Jay, Ling X Zhang, Erin Teeple, Scott McAllister, Gary J Badger, Tannin A Schmidt, Braden C Fleming
BACKGROUND: Lubricin, or proteoglycan 4 (PRG4), is a glycoprotein responsible for joint boundary lubrication. PRG4 has been shown previously to be down-regulated after traumatic joint injury such as a meniscal tear. Preliminary evidence suggests that intra-articular injection of PRG4 after injury will reduce cartilage damage in rat models of surgically induced posttraumatic osteoarthritis. OBJECTIVE: To determine the efficacy of intra-articular injection of full-length recombinant human lubricin (rhPRG4) for reducing cartilage damage after medial meniscal destabilization (DMM) in a preclinical large animal model...
June 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28100421/osteoarthritis-year-in-review-2016-biology
#16
REVIEW
E N Blaney Davidson, A P M van Caam, P M van der Kraan
This review highlights a selection of literature in the area of osteoarthritis biology published between the 2015 and 2016 Osteoarthritis Research Society International (OARSI) World Congress. Highlights were selected from a pubmed search covering cartilage, bone, inflammation and pain. A personal selection was made based, amongst other things, on topics presented during the 2015 conference. This covers circadian rhythm, TGF-β signaling, autophagy, SIRT6, exercise, lubricin, TLR's, pain and NGF. Furthermore, in this review we have made an effort to connect these seemingly distant topics into one scheme of connections between them, revealing a theoretical big picture underneath...
December 17, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28069163/sub-critical-impact-inhibits-the-lubricating-mechanisms-of-articular-cartilage
#17
Edward D Bonnevie, Michelle L Delco, Devis Galesso, Cynthia Secchieri, Lisa A Fortier, Lawrence J Bonassar
Although post-traumatic osteoarthritis accounts for a significant proportion of all osteoarthritis, the understanding of both biological and mechanical phenomena that lead to cartilage degeneration in the years to decades after trauma is still lacking. In this study, we evaluate how cartilage lubrication is altered after a sub-critical impact (i.e., an impact to the cartilage surface that produces surface cracking but not full thickness fissuring). Through utilizing a Stribeck-like framework, the elastoviscous transition, we evaluated changes to both the innate boundary lubricating ability of cartilage after impact and also the effectiveness of high viscosity lubricants to lower friction after impact...
February 28, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/27993210/recombinant-human-lubricin-for-prevention-of-postoperative-intra-abdominal-adhesions-in-a-rat-model
#18
Jaewook Oh, Kean G Kuan, Leong U Tiong, Markus I Trochsler, Gregory Jay, Tannin A Schmidt, Harry Barnett, Guy J Maddern
BACKGROUND: Postoperative intra-abdominal adhesions are a major cause of morbidity and mortality and contribute to a heavy burden on health care resources. At present, numerous introduced adhesion prevention products have demonstrated some benefit but none are consistently effective. The aim of this study was to examine the effectiveness of recombinant human lubricin in preventing intra-abdominal adhesion formation. MATERIALS AND METHODS: A total of 62 male Wistar Albino rats were randomly assigned to the study...
February 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/27853940/novel-role-of-ccn3-that-maintains-the-differentiated-phenotype-of-articular-cartilage
#19
Danilo Janune, Tarek Abd El Kader, Eriko Aoyama, Takashi Nishida, Yasuhiko Tabata, Satoshi Kubota, Masaharu Takigawa
Knowledge of the microenvironment of articular cartilage in health and disease is the key to accomplishing fundamental disease-modifying treatments for osteoarthritis. The proteins comprising the CCN Family are matricellular proteins with a remarkable relevance within the context of cartilage metabolism. CCN2 displays a great capability for regenerating articular cartilage, and CCN3 has been shown to activate the expression of genes related to articular chondrocytes and to repress genes related to endochondral ossification in epiphyseal chondrocytes...
November 16, 2016: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/27824284/formation-of-hyaline-cartilage-tissue-by-passaged-human-osteoarthritic-chondrocytes
#20
Vanessa J Bianchi, Joanna F Weber, Stephen D Waldman, David Backstein, Rita A Kandel
OBJECTIVE: When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are to be used successfully. Transforming growth factor beta (TGFβ) family members are known to be crucial for regulating differentiation of fetal limb mesenchymal cells and mesenchymal stromal cells to chondrocytes...
February 2017: Tissue Engineering. Part A
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