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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
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
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
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
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
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
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
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
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
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
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
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
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
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)...
July 20, 2016: Modern Rheumatology
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
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
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
Ryu Yoshida, Farhang Alaee, Felix Dyrna, Mark S Kronenberg, Peter Maye, Ivo Kalajzic, David W Rowe, Augustus D Mazzocca, Nathaniel A Dyment
Purpose of this study: To elucidate the origin of cell populations that contribute to rotator cuff healing, we developed a mouse surgical model where a full-thickness, central detachment is created in the supraspinatus. MATERIALS AND METHODS: Three different inducible Cre transgenic mice with Ai9-tdTomato reporter expression (PRG4-9, αSMA-9, and AGC-9) were used to label different cell populations in the shoulder. The defect was created surgically in the supraspinatus. The mice were injected with tamoxifen at surgery to label the cells and sacrificed at 1, 2, and 5 weeks postoperatively...
November 2016: Connective Tissue Research
Till E Bechtold, Cheri Saunders, Rebekah S Decker, Hyo-Bin Um, Naiga Cottingham, Imad Salhab, Naito Kurio, Paul C Billings, Maurizio Pacifici, Hyun-Duck Nah, Eiki Koyama
The temporomandibular joint (TMJ) is a diarthrodial joint that relies on lubricants for frictionless movement and long-term function. It remains unclear what temporal and causal relationships may exist between compromised lubrication and onset and progression of TMJ disease. Here we report that Proteoglycan 4 (Prg4)-null TMJs exhibit irreversible osteoarthritis-like changes over time and are linked to formation of ectopic mineralized tissues and osteophytes in articular disc, mandibular condyle and glenoid fossa...
May 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Yusuke Nakagawa, Takeshi Muneta, Koji Otabe, Nobutake Ozeki, Mitsuru Mizuno, Mio Udo, Ryusuke Saito, Katsuaki Yanagisawa, Shizuko Ichinose, Hideyuki Koga, Kunikazu Tsuji, Ichiro Sekiya
OBJECTIVE: Lubricin expression in the superficial cartilage will be a crucial factor in the success of cartilage regeneration. Mesenchymal stem cells (MSCs) are an attractive cell source and the use of aggregates of MSCs has some advantages in terms of chondrogenic potential and efficiency of cell adhesion. Lubricin expression in transplanted MSCs has not been fully elucidated so far. Our goals were to determine (1) whether cartilage pellets of human MSCs expressed lubricin in vitro chondrogenesis, (2) whether aggregates of human MSCs promoted lubricin expression, and (3) whether aggregates of MSCs expressed lubricin in the superficial cartilage after transplantation into osteochondral defects in rats...
2016: PloS One
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