Shirai, T. et al. Chondroprotective effect of alendronate in a rabbit model of osteoarthritis. J. Orthop. Res. 29, 1572-1577

Department of Orthopedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto 606-8507, Japan.
Journal of Orthopaedic Research (Impact Factor: 2.99). 10/2011; 29(10):1572-7. DOI: 10.1002/jor.21394
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ABSTRACT The aim of this study was to determine how alendronate (ALN) alters cartilage degeneration and periarticular bone quality in a rabbit anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA). Thirty rabbits underwent an ACLT on the left knee and a sham operation on the right knee. Fifteen rabbits received weekly subcutaneous injections of ALN (0.14 mg/kg) and 15 rabbits (the control [cont] group) received saline. Animal knees were divided into four groups: cont/sham, cont/ACLT, ALN/sham, and ALN/ACLT. Histological, radiological, and immunohistochemical indices were evaluated for each group. Bone volume ratios by micro-computed tomography showed that ALN prevented periarticular bone loss. Histologically, the cont/ACLT group had significantly worse cartilage damage than the cont/sham group 12 weeks after the surgery. However, the ALN/ACLT group had mild cartilage degeneration compared with that of the ALN/sham group. Immunohistochemical analysis showed that ALN suppressed the expression of matrix metalloproteinase-13, interleukin-1β, type-X collagen, vascular endothelial growth factor, and receptor activator of nuclear factor κB ligand in OA cartilage. ALN had a chondroprotective effect in an experimental rabbit model of OA.

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Available from: Takashi Nakamura, Jan 07, 2014
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    • "The surgically induced models (joint instability) produce a gradual progression of the degenerative changes in the joint that mimic the pathogenesis and pathology of the human traumatic OA [30,31]. The rabbit model was extensively used for testing potential chondroprotective agents including bisphosphonates [18,32] and glucosamine [4,33]. Previously published data showed that most rabbits with anterior cruciate ligament transection develop cartilage degeneration [33,34] and subchondral bone alterations [33] as soon as 8 weeks postsurgery. "
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    ABSTRACT: The osteoarthritis (OA) treatment in humans and in animals is a major orthopaedic challenge because there is not an ideal drug for preserving the joint structure and function. The aim of this study was to assess the effects of the treatment with oral glucosamine and risedronate alone or in combination on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of OA. Osteoarthritis was surgically induced on one knee of 32 New Zealand White rabbits using the contralateral as healthy controls. Three weeks later treatments were started and lasted 8 weeks. Animal were divided in four groups of oral treatment: the first group received only saline, the second 21.5 mg/kg/day of glucosamine sulfate, the third 0.07 mg/kg/day of risedronate; and the fourth group both drugs simultaneously at the same dosages. Following sacrifice femurs were removed and osteochondral cylinders and synovial membrane were obtained for its histological and micro-CT evaluation. Sample analysis revealed that the model induced osteoarthritic changes in operated knees. OA placebo group showed a significant increase in cartilage thickness respect to the control and inflammatory changes in synovial membrane; whereas subchondral bone structure and volumetric bone mineral density remained unchanged. All the treated animals showed an improvement of the cartilage swelling independent of the drug used. Treatment with glucosamine alone seemed to have no effect in the progression of cartilage pathology while risedronate treatment had better results in superficial fibrillation and in resolving the inflammatory changes of the tissues, as well as modifying the orientation of trabecular lattice. The combination of both compounds seemed to have additive effects showing better results than those treated with only one drug. The results of this animal study suggested that glucosamine sulfate and risedronate treatment alone or in combination may be able to stop cartilage swelling. The risedronate treatment could partially stop the fibrillation and the inflammation of synovial membrane as well as modify the orientation of trabeculae in healthy and in osteoarthritic knees.
    BMC Veterinary Research 04/2014; 10(1):97. DOI:10.1186/1746-6148-10-97 · 1.78 Impact Factor
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    • "Rabbit (Oryctolagus cuniculus) The lagomorph species of O. cuniculus has a considerable relevance in the study of osteoarthritis. Osteoarthritis is usually surgically induced (Laverty et al. 2010) and beneficial effects of pharmaceutical substances such as doxycycline or alendronate (Shirai et al. 2011; Pinney et al. 2012) and alternative treatment approaches, for example light emitting diodes, venom factors from bees or Chinese herbs (Chen et al. 2011; Oshima et al. 2011; Ozlem Nisbet et al. 2011) are evaluated. The relevance of rabbit models for asthma research has been underlined by an outstanding publication which first described the potential of antisense oligodeoxynucleotide treatment in allergic diseases in rabbits (Nyce and Metzger 1997). "
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    ABSTRACT: Experimental animals in biomedical research provide insights into disease mechanisms and models for determining the efficacy and safety of new therapies and for discovery of corresponding biomarkers. Although mouse and rat models are most widely used, observations in these species cannot always be faithfully extrapolated to human patients. Thus, a number of domestic species are additionally used in specific disease areas. This review summarizes the most important applications of domestic animal models and emphasizes the new possibilities genetic tailoring of disease models, specifically in pigs, provides.
    Reproduction in Domestic Animals 08/2012; 47 Suppl 4(s4):59-71. DOI:10.1111/j.1439-0531.2012.02056.x · 1.52 Impact Factor
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    • "We have no clear explanation for this result. A study has shown that the lateral components of the rabbit knees were more susceptible to degeneration than the medial components in the ACLMT model [31]. The rabbit knee joints are physiologically in the valgus position, causing excess load on the lateral side, which might explain the susceptibility. "
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    ABSTRACT: Osteoarthritis (OA) is a common cause of disability in older adults. We have previously reported that an agonist for subtypes EP2 of the prostaglandin E2 receptor (an EP2 agonist) promotes the regeneration of chondral and osteochondral defects. The purpose of the current study is to analyze the effect of this agonist on articular cartilage in a model of traumatic degeneration. The model of traumatic degeneration was established through transection of the anterior cruciate ligament and partial resection of the medial meniscus of the rabbits. Rabbits were divided into 5 groups; G-S (sham operation), G-C (no further treatment), G-0, G-80, and G-400 (single intra-articular administration of gelatin hydrogel containing 0, 80, and 400 μg of the specific EP2 agonist, ONO-8815Ly, respectively). Degeneration of the articular cartilage was evaluated at 2 or 12 weeks after the operation. ONO-8815Ly prevented cartilage degeneration at 2 weeks, which was associated with the inhibition of matrix metalloproteinase-13 (MMP-13) expression. The effect of ONO-8815Ly failed to last, and no effects were observed at 12 weeks after the operation. Stimulation of prostaglandin E2 (PGE2) via EP2 prevents degeneration of the articular cartilage during the early stages. With a system to deliver it long term, the EP2 agonist could be a new therapeutic tool for OA.
    Arthritis research & therapy 09/2011; 13(5):R146. DOI:10.1186/ar3460 · 3.75 Impact Factor
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