Disposition of Human Recombinant Lubricin in Naive Rats and in a Rat Model of Post-traumatic Arthritis After Intra-articular or Intravenous Administration

3区 · 医学

Article

作者: Jian Li ; Moisés A. Rivera-Bermúdez ; Xin Xu ; Qin Wang ; John Harrold ; Carl R. Flannery ; Daren Daugusta ; Richard Zollner ; Yulia Vugmeyster

We have recently demonstrated that intra-articular (IA) administration of human recombinant lubricin, LUB:1, significantly inhibited cartilage degeneration and pain in the rat meniscal tear model of post-traumatic arthritis. In this report, we show that after a single IA injection to naïve rats and rats that underwent unilateral meniscal tear, [(125)I]LUB:1 had a tri-phasic disposition profile, with the alpha, beta, and gamma half-life estimates of 4.5 h, 1.5 days, and 2.1 weeks, respectively. We hypothesize that the terminal phase kinetics was related to [(125)I]LUB:1 binding to its ligands. [(125)I]LUB:1 was detected on articular cartilage surfaces as long as 28 days after single IA injection. Micro-autoradiography analysis suggested that [(125)I]LUB:1 tended to localize to damaged joint surfaces in rats with meniscal tear. After a single intravenous (IV) dose to rats, [(125)I]LUB:1 was eliminated rapidly from the systemic circulation, with a mean total body clearance of 154 mL/h/kg and a mean elimination half-life (t (1/2)) of 6.7 h. Overall, LUB:1 has met a desired disposition profile of a potential therapeutic intended for an IA administration: target tissue (knee) retention and fast elimination from the systemic circulation after a single IA or IV dose.

2010-09-01·Letters in Applied Microbiology4区 · 生物学

LuB-1 in rapid toxicity assay

4区 · 生物学

Article

作者: Y. Hong ; Z. Chen ; B. Zhang ; Q. Zhai

AIMSTo isolate marine bacteria with strong bioluminescence in a wide range of NaCl concentration, especially at low salt conditions.METHODS AND RESULTSA luminous bacterium named LuB-1 was isolated from China. It was identified by biochemical analysis and phylogenetic analysis based on the 16S rRNA gene and designated as Photobacterium sp. The isolate is capable of emitting strong and stable luminescence in a wide range of NaCl concentration from 0.2 to 5% (w/v). For most toxic agents tested in this study, the response of LuB-1 was better than that of MicrotoxVibrio fischeri under both low salt (0.9% NaCl) and high salt (2.0% NaCl) conditions.CONCLUSIONThe strain LuB-1 had an obvious predominance of bioluminescence in a wide range of NaCl concentration and better response for heavy metal pollutants and some organic toxicants in both low and high salt toxicity test systems.SIGNIFICANCE AND IMPACT OF THE STUDYBecause of its good sensitivity in a wide range of salt concentration, the strain LuB-1 should have its unique advantage in rapid assay for toxicants in water with different salt concentrations.

2009-03-01·Arthritis & Rheumatism

Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin

Article

作者: Jason P. Gleghorn ; Sonya S. Glasson ; Aled R. Jones ; Alison M. Bendele ; Tracey Blanchet ; Richard Zollner ; Elisabeth A. Morris ; Adam Root ; Chris Corcoran ; Lawrence J. Bonassar ; Carl R. Flannery ; Moisés A. Rivera-Bermúdez

AbstractObjectiveLubricin, also referred to as superficial zone protein and PRG4, is a synovial glycoprotein that supplies a friction‐resistant, antiadhesive coating to the surfaces of articular cartilage, thereby protecting against arthritis‐associated tissue wear and degradation. This study was undertaken to generate and characterize a novel recombinant lubricin protein construct, LUB:1, and to evaluate its therapeutic efficacy following intraarticular delivery in a rat model of osteoarthritis (OA).MethodsBinding and localization of LUB:1 to cartilage surfaces was assessed by immunohistochemistry. The cartilage‐lubricating properties of LUB:1 were determined using a custom friction testing apparatus. A cell‐binding assay was performed to quantify the ability of LUB:1 to prevent cell adhesion. Efficacy studies were conducted in a rat meniscal tear model of OA. One week after the surgical induction of OA, LUB:1 or phosphate buffered saline vehicle was administered by intraarticular injection for 4 weeks, with dosing intervals of either once per week or 3 times per week. OA pathology scores were determined by histologic analysis.ResultsLUB:1 was shown to bind effectively to cartilage surfaces, and facilitated both cartilage boundary lubrication and inhibition of synovial cell adhesion. Treatment of rat knee joints with LUB:1 resulted in significant disease‐modifying, chondroprotective effects during the progression of OA, by markedly reducing cartilage degeneration and structural damage.ConclusionOur findings demonstrate the potential use of recombinant lubricin molecules in novel biotherapeutic approaches to the treatment of OA and associated cartilage abnormalities.

100 项与 LUB-001 相关的药物交易

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