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R D Chavez, G Coricor, J Perez, H-S Seo, R Serra
OBJECTIVE: We previously identified PAPSS2 as a transcriptional target of 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, PRG4. In this study, TGF-β-mediated regulation of SOX9 was characterized, and the involvement of SOX9 in regulation of PAPSS2 mRNA was investigated...
October 13, 2016: 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...
September 23, 2016: 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 injurious impact. Trauma was initiated through impaction on talar cartilage explants. Articulation and loading were applied in a joint bioreactor over five consecutive days. The early (24 hrs) effects of impaction included 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...
August 23, 2016: 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)...
August 4, 2016: 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...
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 Interkeukin-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...
July 13, 2016: 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...
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...
May 16, 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
Devin B Lemmex, Yohei Ono, Carol R Reno, David A Hart, Ian K Y Lo, Gail M Thornton
This study investigated whether ovariohysterectomy (OVH) surgery to induce menopause resulted in changes to modulus, failure strain and lubricin/proteoglycan 4 (PRG4) gene expression in rabbit medial collateral ligaments (MCLs), similar to aging (Thornton et al., 2015a). The MCLs from adult rabbits that underwent OVH surgery as adolescents (15-week-old) and adults (1-year-old) were compared by evaluating mechanical behaviour (adolescent OVH, n=8; adult OVH, n=7; normal, n=7), gene expression (adolescent OVH, n=9; adult OVH, n=8; normal, n=8), and collagen and glycosaminoglycan (adolescent OVH, n=9; adult OVH, n=8; normal, n=8) and water (adolescent OVH, n=9; adult OVH, n=8; normal, n=8) content...
February 8, 2016: Journal of Biomechanics
Ali Alquraini, Steven Garguilo, Gerard D'Souza, Ling X Zhang, Tannin A Schmidt, Gregory D Jay, Khaled A Elsaid
BACKGROUND: Lubricin/proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 has a homeostatic multifaceted role in the joint. PRG4 intra-articular treatment retards progression of cartilage degeneration in pre-clinical posttraumatic osteoarthritis models. The objective of this study is to evaluate the binding of recombinant human PRG4 (rhPRG4) and native human PRG4 (nhPRG4) to toll-like receptors 2 and 4 (TLR2 and TLR4) and whether this interaction underpins a PRG4 anti-inflammatory role in synovial fluid (SF) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA)...
December 4, 2015: Arthritis Research & Therapy
Saleem Abubacker, Dragana Ponjevic, Hyun O Ham, Phillip B Messersmith, John R Matyas, Tannin A Schmidt
PURPOSE: The objectives of this study were to assess the cartilage boundary lubricating ability of (1) nonreduced (NR) disulfide-bonded proteoglycan 4 (PRG4) multimers versus PRG4 monomers and (2) NR versus reduced and alkylated (R/A) PRG4 monomers and to assess (3) the ability of NR PRG4 multimers versus monomers to adsorb to an articular cartilage surface. MATERIALS AND METHODS: PRG4 was separated into two preparations, PRG4 multimer enriched (PRG4Multi+) and PRG4 multimer deficient (PRG4Multi-), using size exclusion chromatography (SEC) and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)...
2016: Connective Tissue Research
T E Bechtold, C Saunders, C Mundy, H Um, R S Decker, I Salhab, N Kurio, P C Billings, M Pacifici, H D Nah, E Koyama
Heterotopic cartilage develops in certain pathologic conditions, including those affecting the human temporomandibular joint (TMJ), but the underlying molecular mechanisms remain obscure. This is in part due to the fact that a reliable animal model of such TMJ diseases is not available. Here, we show that aberrant chondrocyte differentiation and ectopic cartilage formation occur spontaneously in proteoglycan 4 (Prg4) mutant TMJ discs without further invasive procedure. By 2 mo of age, mutant disc cells displayed chondrocyte transdifferentiation, accompanied by strong expression of cartilage master gene Sox9 and matrix genes aggrecan and type II collagen...
March 2016: Journal of Dental Research
Kang-Yun Lee, Hsiao-Chi Chuang, Tzu-Tao Chen, Wen-Te Liu, Chien-Ling Su, Po-Hao Feng, Ling-Ling Chiang, Mauo-Ying Bien, Shu-Chuan Ho
INTRODUCTION: The measurement of C-reactive protein (CRP) to confirm the stability of COPD has been reported. However, CRP is a systemic inflammatory biomarker that is related to many other diseases. OBJECTIVE: The objective of this study is to discover a diagnostic biomarker for COPD. METHODS: Sixty-one subjects with COPD and 15 healthy controls (10 healthy non-smokers and 5 smokers) were recruited for a 1-year follow-up study. Data regarding the 1-year acute exacerbation frequency and changes in lung function were collected...
2015: International Journal of Chronic Obstructive Pulmonary Disease
Kosaku Sawada, Jordi Caballé-Serrano, Dieter D Bosshardt, Benoit Schaller, Richard J Miron, Daniel Buser, Reinhard Gruber
AIM: Chemical decontamination increases the availability of bone grafts; however, it remains unclear whether antiseptic processing changes the biological activity of bone. MATERIALS AND METHODS: Bone chips were incubated with four different antiseptic solutions including (1) povidone-iodine (0.5%), (2) chlorhexidine diguluconate (0.2%), (3) hydrogen peroxide (1%) and (4) sodium hypochlorite (0.25%). After 10 min. of incubation, changes in the capacity of the bone-conditioned medium (BCM) to modulate gene expression of gingival fibroblasts was investigated...
September 2015: Journal of Clinical Periodontology
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