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https://www.readbyqxmd.com/read/28482921/the-autocrine-role-of-proteoglycan-4-prg4-in-modulating-osteoarthritic-synoviocyte-proliferation-and-expression-of-matrix-degrading-enzymes
#1
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/28462005/inhibitors-of-dna-methylation-support-tgf-%C3%AE-1-induced-il11-expression-in-gingival-fibroblasts
#2
Irina-Georgeta Sufaru, Gabriel Beikircher, Andreas Weinhaeusel, Reinhard Gruber
PURPOSE: Oral wound healing requires gingival fibroblasts to respond to local growth factors. Epigenetic silencing through DNA methylation can potentially decrease the responsiveness of gingival fibroblasts to local growth factors. In this study, our aim was to determine whether the inhibition of DNA methylation sensitized gingival fibroblasts to transforming growth factor-β1 (TGF-β1). METHODS: Gingival fibroblasts were exposed to 5-aza-2'-deoxycytidine (5-aza), a clinically approved demethylating agent, before stimulation with TGF-β1...
April 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/28438606/cell-origin-volume-and-arrangement-are-drivers-of-articular-cartilage-formation-morphogenesis-and-response-to-injury-in-mouse-limbs
#3
Rebekah S Decker, Hyo-Bin Um, Nathaniel A Dyment, Naiga Cottingham, Yu Usami, Motomi Enomoto-Iwamoto, Mark S Kronenberg, Peter Maye, David W Rowe, Eiki Koyama, Maurizio Pacifici
Limb synovial joints are composed of distinct tissues, but it is unclear which progenitors produce those tissues and how articular cartilage acquires its functional postnatal organization characterized by chondrocyte columns, zone-specific cell volumes and anisotropic matrix. Using novel Gdf5(CreERT2) (Gdf5-CE), Prg4-CE and Dkk3-CE mice mated to R26-Confetti or single-color reporters, we found that knee joint progenitors produced small non-migratory progenies and distinct local tissues over prenatal and postnatal time...
April 21, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28371297/the-differential-plasma-proteome-of-obese-and-overweight-individuals-undergoing-a-nutritional-weight-loss-and-maintenance-intervention
#4
Sergio Oller Moreno, Ornella Cominetti, Antonio Núñez Galindo, Irina Irincheeva, John Corthésy, Arne Astrup, Wim H M Saris, Jörg Hager, Martin Kussmann, Loïc Dayon
PURPOSE: The nutritional intervention program "DiOGenes" focuses on how obesity can be prevented and treated from a dietary perspective. We generated differential plasma proteome profiles in the DiOGenes cohort to identify proteins associated with weight loss and maintenance and explore their relation to body mass index, fat mass, insulin resistance and sensitivity. EXPERIMENTAL DESIGN: Relative protein quantification was obtained at baseline and after combined weight loss/maintenance phases using isobaric tagging and MS/MS...
March 29, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28291008/the-efficacy-of-yttrium-90-radiosynovectomy-in-patients-with-camptodactyly-arthropathy-coxa-vara-pericarditis-syndrome
#5
Sulaiman Mohammed Al-Mayouf, Nora Almutairi, Khalid Alismail
OBJECTIVE: Camptodactyly-arthropathy-coxa-vara-pericarditis (CACP) syndrome is an autosomal recessive disorder caused by mutations in PRG4 gene that encodes for proteoglycan 4, the main lubricant for joints and tendon surfaces. It is a non-inflammatory arthropathy, characterized by joint effusions and synovial hypertrophy. So far, there is no effective treatment for this disorder. To evaluate the effectiveness of yttrium-90 radiosynovectomy in arthropathy of patients with CACP syndrome...
February 5, 2017: Molecular Imaging and Radionuclide Therapy
https://www.readbyqxmd.com/read/28266618/confocal-imaging-of-mouse-mandibular-condyle-cartilage
#6
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/28192118/prg4-expression-in-myxoid-liposarcoma-maintains-tumor-cell-growth-through-suppression-of-an-antitumor-cytokine-il-24
#7
Kosuke Oikawa, Anna Mizusaki, Masakatsu Takanashi, Takashi Ozaki, Fuyuki Sato, Masahiko Kuroda, Yasuteru Muragaki
PRG4 is one of the downstream molecules of the myxoid liposarcoma (MLS)-specific fusion oncoproteins TLS-CHOP and EWS-CHOP. Exogenous PRG4 expression increases the tumorigenicity of cells injected in nude mice. The molecular functions of PRG4 in tumorigenesis and/or tumor progression of MLS cells, however, still remain unclear. In this report, we demonstrated that siRNA-mediated knockdown of PRG4 suppressed the growth of the MLS-derived cell lines 1955/91 and 2645/94. In addition, PRG4 knockdown promoted adipocytic differentiation in 1955/91 cells...
March 25, 2017: Biochemical and Biophysical Research Communications
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
#8
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...
January 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/27911782/egfr-signaling-is-critical-for-maintaining-the-superficial-layer-of-articular-cartilage-and-preventing-osteoarthritis-initiation
#9
Haoruo Jia, Xiaoyuan Ma, Wei Tong, Basak Doyran, Zeyang Sun, Luqiang Wang, Xianrong Zhang, Yilu Zhou, Farid Badar, Abhishek Chandra, X Lucas Lu, Yang Xia, Lin Han, Motomi Enomoto-Iwamoto, Ling Qin
Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox)...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27746378/sox9-protein-is-stabilized-by-tgf-%C3%AE-and-regulates-papss2-mrna-expression-in-chondrocytes
#10
R D Chavez, G Coricor, J Perez, H-S Seo, R Serra
OBJECTIVE: We previously identified 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) as a transcriptional target of transforming growth factor β (TGF-β) in chondrocytes. PAPSS2 is required for proper sulfation of proteoglycans in cartilage. Defective sulfation in the matrix results in alterations in mechanical properties of the cartilage that would be expected to result in degeneration. The objective of this study was to identify factors that regulate PAPSS2 expression and compare to a known TGF-β responsive gene, proteoglycan 4/lubricin (PRG4)...
February 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27688846/modulation-of-superficial-zone-protein-lubricin-prg4-by-kartogenin-and-transforming-growth-factor-%C3%AE-1-in-surface-zone-chondrocytes-in-bovine-articular-cartilage
#11
Kazumasa Miyatake, Kenjiro Iwasa, Sean M McNary, Gordon Peng, A Hari Reddi
OBJECTIVE: Superficial zone protein (SZP)/lubricin/PRG4 functions as a boundary lubricant in articular cartilage to decrease friction and wear. As articular cartilage lubrication is critical for normal joint function, the accumulation of SZP at the surface of cartilage is important for joint homeostasis. Recently, a heterocyclic compound called kartogenin (KGN) was found to induce chondrogenic differentiation and enhance mRNA expression of lubricin. The objective of this study was to determine whether KGN can stimulate synthesis of SZP in superficial zone, articular chondrocytes...
October 2016: Cartilage
https://www.readbyqxmd.com/read/27658527/pxl01-in-sodium-hyaluronate-results-in-increased-prg4-expression-a-potential-mechanism-for-anti-adhesion
#12
Sara Edsfeldt, Björn Holm, Margit Mahlapuu, Carol Reno, David A Hart, Monica Wiig
PURPOSE: To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility. MATERIALS AND METHODS: On days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair...
March 2017: Upsala Journal of Medical Sciences
https://www.readbyqxmd.com/read/27626040/treatment-of-osteoarthritis-using-a-helper-dependent-adenoviral-vector-retargeted-to-chondrocytes
#13
Merry Zc Ruan, Vincenzo Cerullo, Racel Cela, Chris Clarke, Evy Lundgren-Akerlund, Michael A Barry, Brendan Hl Lee
Osteoarthritis (OA) is a joint disease characterized by degeneration of the articular cartilage, subchondral bone remodeling, and secondary inflammation. It is among the top three causes of chronic disability, and currently there are no treatment options to prevent disease progression. The localized nature of OA makes it an ideal candidate for gene and cell therapy. However, gene and cell therapy of OA is impeded by inefficient gene transduction of chondrocytes. In this study, we developed a broadly applicable system that retargets cell surface receptors by conjugating antibodies to the capsid of helper-dependent adenoviral vectors (HDVs)...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27551813/implications-of-trauma-and-subsequent-articulation-on-the-release-of-proteoglycan-4-and-tissue-response-in-adult-human-ankle-cartilage
#14
Vivek K Shekhawat, Thomas M Schmid, Peter H Pennekamp, Carol A Pacione, Susan Chubinskaya, Markus A Wimmer
The purpose of this study was to investigate the effects of trauma and subsequent articulation on adult human ankle cartilage subjected to an injurious impact. Trauma was initiated through impaction on talar cartilage explants. Articulation and loading were applied in a joint bioreactor over 5 consecutive days. The early (24 h) effects of impaction included a reduced chondrocytes viability (51% vs. 81% for non-impacted; p = 0.03), increased levels of apoptosis (43% vs. 27%; p = 0.03), and an increase in the histopathology score (4...
March 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/27498214/lubricin-proteoglycan-4-increases-in-both-experimental-and-naturally-occurring-equine-osteoarthritis
#15
H L Reesink, A E Watts, H O Mohammed, G D Jay, A J Nixon
OBJECTIVE: The goals of this study were (1) to quantify proteoglycan 4 (PRG4) gene expression; (2) to assess lubricin immunostaining; and (3) to measure synovial fluid lubricin concentrations in clinical and experimental models of equine carpal osteoarthritis (OA). DESIGN: Lubricin synovial fluid concentrations and cartilage and synovial membrane PRG4 expression were analyzed in research horses undergoing experimental OA induction (n = 8) and in equine clinical patients with carpal OA (n = 58)...
January 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27472842/rheological-effects-of-macromolecular-interactions-in-synovial-fluid
#16
REVIEW
L Martin-Alarcon, T A Schmidt
The rheological properties of synovial fluid (SF) are largely attributed to the presence of high molecular weight hyaluronan (HA). However, rheological differences between SF and pure HA solutions suggest that SF proteins actively contribute towards the bulk viscoelasticity of this biological fluid. Due to various experimental challenges involved with the rheometry of low-viscosity biological fluids, the macromolecular interactions in SF and their relative rheological importance are still a matter of active discussion...
July 29, 2016: Biorheology
https://www.readbyqxmd.com/read/27435056/association-of-lubricin-concentration-in-synovial-fluid-and-clinical-status-of-osteoarthritic-knee
#17
Hiroyasu Ogawa, Kazu Matsumoto, Nobuo Terabayashi, Kenji Kawashima, Kentaro Takeuchi, Haruhiko Akiyama
OBJECTIVES: Although lubricin plays a role in controlling inflammation and pain as well as being a mechanical lubricant, clinical relevance of lubricin concentration in synovial fluid (SF) is unknown. The purpose was to determine whether lubricin concentration in SF is associated with the clinical status of the knee. METHODS: SF was obtained from 61 knee joints from patients who underwent any knee surgery with several stages of knee osteoarthritis. Lubricin/PRG4 concentration in SF was measured by enzyme-linked immunosorbent assay (ELISA)...
May 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/27434666/ancient-origin-of-lubricated-joints-in-bony-vertebrates
#18
Amjad Askary, Joanna Smeeton, Sandeep Paul, Simone Schindler, Ingo Braasch, Nicholas A Ellis, John Postlethwait, Craig T Miller, J Gage Crump
Synovial joints are the lubricated connections between the bones of our body that are commonly affected in arthritis. It is assumed that synovial joints first evolved as vertebrates came to land, with ray-finned fishes lacking lubricated joints. Here, we examine the expression and function of a critical lubricating protein of mammalian synovial joints, Prg4/Lubricin, in diverse ray-finned fishes. We find that Prg4 homologs are specifically enriched at the jaw and pectoral fin joints of zebrafish, stickleback, and gar, with genetic deletion of the zebrafish prg4b gene resulting in the same age-related degeneration of joints as seen in lubricin-deficient mice and humans...
July 19, 2016: ELife
https://www.readbyqxmd.com/read/27411036/reduction-of-friction-by-recombinant-human-proteoglycan-4-in-il-1%C3%AE-stimulated-bovine-cartilage-explants
#19
Katherine M Larson, Ling Zhang, Khaled A Elsaid, Tannin A Schmidt, Braden C Fleming, Gary J Badger, Gregory D Jay
A boundary lubricant attaches and protects sliding bearing surfaces by preventing interlocking asperity-asperity contact. Proteoglycan-4 (PRG4) is a boundary lubricant found in the synovial fluid that provides chondroprotection to articular surfaces. Inflammation of the diarthrodial joint modulates local PRG4 concentration. Thus, we measured the effects of inflammation, with Interleukin-1α (IL-1α) incubation, upon boundary lubrication and PRG4 expression in bovine cartilage explants. We further aimed to determine whether the addition of exogenous human recombinant PRG4 (rhPRG4) could mitigate the effects of inflammation on boundary lubrication and PRG4 expression in vitro...
March 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/27224999/protein-losing-enteropathy-in-camptodactyly-arthropathy-coxa-vara-pericarditis-cacp-syndrome
#20
Bram Peters, Janneke H M Schuurs-Hoeijmakers, Joris Fuijkschot, Annette Reimer, Michiel van der Flier, Dorien Lugtenberg, Esther P A H Hoppenreijs
BACKGROUND: Camptodactyly-arthropathy-coxa vara-pericarditis (CACP, OMIM: #208250) syndrome is a rare autosomal recessive disease that can be difficult to recognise not only because of its wide clinical variability but also because of its clinical resemblance to juvenile idiopathic arthritis (JIA). PRG4 is the only gene so far known to be associated with CACP syndrome. Children with CACP syndrome lack the glycoprotein lubricin due to recessive mutations in PRG4. Lubricin serves as a lubricant in joints, tendons and visceral cavities (pleural cavity, pericardium) and inhibits synovial proliferation...
May 25, 2016: Pediatric Rheumatology Online Journal
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