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Alison M. Bendele

Alison M. Bendele
Bolder BioPATH

40.64
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DVM, PhD, DACVP
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Research items (157)
Article
Current osteoarthritis (OA) research searches for treatments that modify the course of disease progression. Autologous Protein Solution (APS) is derived from whole blood and is a unique autologous therapy that contains high concentrations of white blood cells, platelets, and concentrated plasma, providing cytokines that can target the underlying me...
Article
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As an initial step in the development of a local therapeutic to treat osteoarthritis (OA), a number of agents were tested for their ability to block activation of inflammation through nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), subchondral bone changes through receptor activator of nuclear factor κB ligand (RANKL)-mediated o...
Article
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Objectives: This study was performed to evaluate the potential efficacy of natural eggshell membrane (NEM) in collagen-induced arthritic rats, a well-established rodent model of inflammation and rheumatoid arthritis. Methods: Rats with developing type II collagen-induced arthritis (CIA) were treated once daily by oral gavage on study days -14 to...
Article
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Objective: Investigation of osteoarthritis (OA) risk alleles suggests that reduced levels of growth and differentiation factor-5 (GDF5) may be a precipitating factor in OA. We hypothesized that intra-articular recombinant human GDF5 (rhGDF5) supplementation to the OA joint may alter disease progression. Methods: A rat medial meniscus transection...
Article
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The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is an initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for prolife...
Answer
Dose it @ 10mg/kg Q2D. It will take ~ 5 doses before mice begin to make antibodies to the Enbrel.
Article
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Objective To investigate whether the effects of nerve growth factor (NGF) inhibition with tanezumab on rats with medial meniscal tear (MMT) effectively model rapidly progressive osteoarthritis (RPOA) observed in clinical trials. Methods Male Lewis rats underwent MMT surgery and were treated weekly with tanezumab (0.1, 1 or 10 mg/kg), isotype contr...
Article
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The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath. org/inhand.asp) is an initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for prolif...
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IntroductionCathepsin K (catK) expression is increased in cartilage, bone and synovium during osteoarthritis (OA). To study the role of catK expression and elevated cathepsin activity in the synovium on cartilage destruction in established OA, we over-expressed cystatin C (cysC), a natural cysteine protease inhibitor, in the synovium of rabbit OA j...
Conference Paper
Background/Purpose: The Non-receptor tyrosine kinases, JAK3 and ITK are key regulators of cytokine pathways and are important clinically validated targets, which offer the potential for developing targeted therapeutics in treating Rheumatoid Arthritis (RA) and other immunological, inflammatory and autoimmune diseases such as systemic lupus erythema...
Article
Objective To evaluate the efficacy of a single intra-articular (IA) dose of FX006, an extended release formulation of triamcinolone acetonide (TCA) in poly(lactic-co-glycolic acid) (PLGA) microspheres, on the sequelae of repeated episodes of synovitis. Design Three flares of localized synovitis in the right knee of rats were induced over 4 weeks f...
Article
Current therapeutic treatment options for osteoarthritis entail significant safety concerns. A novel ropivacaine crystalline microsuspension for bolus intra-articular (IA) delivery was thus developed and studied in a peptidoglycan polysaccharide (PGPS)-induced ankle swelling rat model. Compared with celecoxib controls, both oral and IA, ropivacaine...
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Introduction The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferen...
Article
This study compared the effect of intra-tendon (IT) delivery of recombinant human platelet-derived growth factor-BB (rhPDGF-BB), platelet-rich plasma (PRP) and corticosteroids in a rat tendinopathy model. Seven days after collagenase induction of tendinopathy, a 30-µl IT injection was administered. Treatments included: saline; 3 µg rhPDGF-BB; 10 µg...
Article
The purpose of this study was to assess whether intra-tendon delivery of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) would improve Achilles tendon repair in a rat collagenase-induced tendinopathy model. Seven days following collagenase induction of tendinopathy, one of four intra-tendinous treatments was administered: (i) Vehicl...
Article
APPA, a proprietary combination of apocynin and paeonol, was evaluated for inhibition of cartilage destruction in a well-accepted rat model of osteoarthritis. Methods: Male Lewis rats were anesthetized and aseptic procedures utilized to induce a medial meniscal 'tear', under an IACUC-approved protocol. APPA was orally administered at 80mg/kg BID (...
Article
To demonstrate that the novel highly selective matrix metalloproteinase 13 (MMP-13) inhibitor PF152 reduces joint lesions in adult dogs with osteoarthritis (OA) and decreases biomarkers of cartilage degradation. The potency and selectivity of PF152 were evaluated in vitro using 16 MMPs, TACE, and ADAMTS-4 and ADAMTS-5, as well as ex vivo in human c...
Article
During the development of disease-modifying osteoarthritis (OA) drugs, rat models of OA are frequently used for a first assessment of in vivo efficacy. The most efficacious compound in the rat model may then be tested in a larger animal model before entering human trials. The aim of this study was to describe a histologic scoring system for use in...
Article
This review focuses on the criteria for assessing osteoarthritis (OA) in the guinea pig at the macroscopic and microscopic levels, and recommends particular assessment criteria to assist standardization in the conduct and reporting of preclinical trails in guinea pig models of OA. A review was conducted of all OA studies from 1958 until the present...
Article
The mouse model of collagen induced arthritis (CIA) effectively mimics human disease and thus is useful for testing and development of rheumatoid arthritis (RA) therapies. We developed a Ligand Epitope Antigen Presentation System (LEAPS) peptide hetero-conjugate vaccine containing an epitope of human collagen type II (CEL-2000) that acted as a ther...
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Objective Matrix metalloproteinases (MMPs) have long been considered excellent targets for osteoarthritis (OA) treatment. However, clinical utility of broad-spectrum MMP inhibitors developed for this purpose has been restricted by dose-limiting musculoskeletal side effects observed in humans. This study was undertaken to identify a new class of pot...
Article
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Multiple inflammatory mediators in osteoarthritis (OA) cartilage, including S100/calgranulin ligands of receptor for advanced glycation end products (RAGE), promote chondrocyte hypertrophy, a differentiation state associated with matrix catabolism. In this study, we observed that RAGE knockout was not chondroprotective in instability-induced knee O...
Article
Cathepsin K (cat K), a cysteine protease expressed in osteoclasts, chondrocytes and synovial fibroblasts, degrades several bone and cartilage matrix components suggesting its potential role in osteoarthritis (OA). We investigated the effects of SB-553484, an inhibitor of cat K, on lesion severity and biomarkers of collagen degradation in the canine...
Article
Lubricin, 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...
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Murine gammadelta T cell subsets, defined by their Vgamma chain usage, have been shown in various disease models to have distinct functional roles. In this study, we examined the responses of the two main peripheral gammadelta T cell subsets, Vgamma1(+) and Vgamma4(+) cells, during collagen-induced arthritis (CIA), a mouse model that shares many ha...
Article
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Murine T cell subsets, defined by their V chain usage, have been shown in various disease models to have distinct functional roles. In this study, we examined the responses of the two main peripheral T cell subsets, V1 and V4 cells, during collagen-induced arthritis (CIA), a mouse model that shares many hallmarks with human rheumatoid arthritis. We...
Chapter
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Article
Conclusions: This method allows obtain the necessary direct and indirect values to characterize the mechanical behaviour of articular cartilage in rabbit's femoral condyles, showing normal viscoelastic behaviour of the samples. The 19 weeks samples show higher values of instantaneous load, Young and Shear module than 16 weeks samples, because of th...
Article
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Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for a variety of inflammatory conditions; however, the benefits of this class of drugs are accompanied by deleterious side effects, most commonly gastric irritation and ulceration. NSAID-induced ulceration is thought to be exacerbated by intestinal microbiota, but previous studie...
Article
The roles of the transmembrane and secreted forms of tumor necrosis factor α (TNFα) in rheumatoid arthritis (RA) remain unclear. Agents used to inhibit TNFα have shown varying efficacy in RA patients, suggesting that anti-TNFα agents possess dissimilar mechanisms of action, including the ability to neutralize transmembrane (tmTNFα) and secreted TNF...
Article
Osteoarthritis (OA) is the most common form of arthritis and a primary cause of disability, however, there are no treatments that can slow disease progression or repair damaged joint cartilage. Fibroblast growth factor-18 (FGF18) has been reported to have significant anabolic effects on cartilage. We therefore examined its effects on repair of cart...
Article
To determine whether decreases in peak vertical force of the hind limb after transection of the cranial cruciate ligament (CrCL) would be indicative of medial meniscal damage in dogs. 39 purpose-bred adult male Walker Hounds. The right CrCL was transected arthroscopically. Force plate measurements of the right hind limb were made prior to and 2, 4,...
Article
The aim of this study was to determine whether fusion proteins comprising human granulocyte colony-stimulating factor (G-CSF) joined to human immunoglobulin G1 and G4 (IgG1 and IgG4) Fc and C(H) domains are biologically active and have improved pharmacokinetic and hematopoietic properties in vivo. Chimeric genes encoding human G-CSF fused to the N-...
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A recombinant C-terminal truncated form of the human soluble tumor necrosis factor receptor type I (sTNF-RI) was produced in E. coli. This soluble receptor contains the first 2.6 of the 4 domains of the intact sTNF-RI molecule. A monoPEGylated form of this molecule was produced using a 30 kD methoxyPEG aldehyde with approximately 85% selectivity fo...
Article
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The objective of these studies was to examine collagen-induced arthritis (CIA) in C57BL/6 mice transgenic for the rodent complement regulatory protein complement receptor 1-related gene/protein y (Crry) (Crry-Tg), a C3 convertase inhibitor. The scores for clinical disease activity and for histological damage in the joints were both significantly de...
Article
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IL-18 is an important cytokine in autoimmune and inflammatory diseases through the induction of IFN-gamma, TNF-alpha, and IL-1. We report herein that collagen-induced arthritis (CIA) in mice is inhibited by treatment with murine IL-18 binding protein (mIL-18BP). CIA was induced in DBA/1J mice by the injection of bovine type II collagen (CII) in IFA...
Article
Animal models of osteoarthritis (OA) are used to study the pathogenesis of cartilage degeneration and to evaluate potential anti-arthritic drugs for clinical use. In general, these models fall into 2 categories, spontaneous and induced (surgical instability or genetic manipulation). Animal models of naturally occurring OA occur in knee joints of gu...
Article
To determine the mechanisms of amelioration of collagen-induced arthritis (CIA) in DBA/1J mice by inhibition of complement activation. Mice received 2 intradermal injections of bovine type II collagen (CII), on days 0 and 21. From day 21 (immediately after the second injection of CII) through day 35, mice received intraperitoneal injections of eith...
Article
Characterize a model of osteoarthritis (OA) induced by a surgically transecting the medial collateral ligament and meniscus. Evaluate the effectiveness of a matrix metalloproteinase (MMP) inhibitor in this model. The medial collateral ligament of the right knee of rats was transected and a single full thickness cut was made through meniscus. Rats w...
Article
We recently identified a novel member of the human fibroblast growth factor (FGF) family of signaling molecules, designated FGF-20. In the present study, we examined the activity of this protein in 2 animal models of acute intestinal inflammation and in mechanistic studies in vitro. In vivo experiments consisted of a murine dextran sulfate sodium (...
Article
This study examines the effects of an IL-6-producing murine multiple myeloma cell line on trabecular and cortical mouse bone, and evaluates the efficacy of interleukin-1 receptor antagonist (IL-1ra) in mitigating bone destruction. Six-week-old BALB/c mice were assigned to two groups: normal controls and myeloma animals (5 x 10(7) MPC-11 cells on da...
Article
Animal models of osteoarthritis are used to study the pathogenesis of cartilage degeneration and to evaluate potential antiarthritic drugs for clinical use. Animal models of naturally occurring osteoarthritis (OA) occur in knee joints of guinea pigs, mice and other laboratory animal species. Transgenic models have been developed in mice. Commonly u...
Article
Animal models of arthritis are used to study pathogenesis of disease and to evaluate potential anti-arthritic drugs for clinical use. Therefore morphological similarities to human disease and capacity of the model to predict efficacy in humans are important criteria in model selection. Animal models of rheumatoid arthritis (RA) with a proven track...
Article
To determine the potential for additive or synergistic effects of combination therapy with the recombinant anticytokine agents interleukin-1 receptor antagonist (IL-1Ra) and PEGylated soluble tumor necrosis factor receptor type I (PEG sTNFRI) in established type H collagen-induced arthritis (CIA) and developing adjuvant-induced arthritis (AIA) in r...