Mono‐iodoacetate‐induced experimental osteoarthritis. A dose‐response study of loss of mobility, morphology, and biochemistry

Guingamp, Corinne; Gégout-Pottie, Pascale; Philippe, Lionel; Terlain, Bernard; Netter, Patrick; Gillet, Pierre

doi:10.1002/art.1780400917

Cited by 357 publications

(290 citation statements)

References 26 publications

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“…The rat model of monoiodoacetate (MIA)-induced OA (23)(24)(25) was used for assessing the effects of MMP-13 inhibitors on cartilage degradation and joint pain. Male Sprague-Dawley rats weighing 175-200 gm (12 per group) were anesthetized for 1 minute in an inhalation chamber, using a mixture of carbon dioxide and oxygen (60:40), and on day 0 were injected in the right knee joint with 50 l saline containing 1 mg MIA.…”

Section: Methodsmentioning

confidence: 99%

A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models

Baragi

Becher²,

Bendele³

et al. 2009

Arthritis & Rheumatism

152

127

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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 potent and selective MMP-13 inhibitors that would provide histologic and clinical efficacy without musculoskeletal toxicity.Methods. Selectivity assays were developed using catalytic domains of human MMPs. Freshly isolated bovine articular cartilage or human OA cartilage was used in in vitro cartilage degradation assays. The rat model of monoiodoacetate (MIA)-induced OA was implemented for assessing the effects of MMP-13 inhibitors on cartilage degradation and joint pain. The surgical medial meniscus tear model in rats was used to evaluate the chondroprotective ability of MMP-13 inhibitors in a chronic disease model of OA. The rat model of musculoskeletal side effects (MSS) was used to assess whether selective MMP-13 inhibitors have the joint toxicity associated with broad-spectrum MMP inhibitors.Results. A number of non-hydroxamic acidcontaining compounds that showed a high degree of potency for MMP-13 and selectivity against other MMPs were designed and synthesized. Steady-state kinetics experiments and Lineweaver-Burk plot analysis of rate versus substrate concentration with one such compound, ALS 1-0635, indicated linear, noncompeti-

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Section: Methodsmentioning

confidence: 99%

A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models

Baragi

Becher²,

Bendele³

et al. 2009

Arthritis & Rheumatism

152

127

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show abstract

“…The basal readings were established with a group of rats that were injected with saline in their knees. 9 MIA effected directly on the balance of the metabolic activity of chondrocytes and induced a loss of functional properties of cartilage. Energy intake of chondrocytes derived from the physiological process of glycolysis.…”

Section: Osteoarthritis Inductionmentioning

confidence: 99%

Radiographic and Histopathologic Analysis on Osteoarthritis Rat Model Treated with Essential Oils of Rosmarinus officinalis and Populus alba

Belkhodja¹,

Meddah²,

Tirtouil³

et al. 2017

Pharm Sci

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“…MIA is an inhibitor of glyceraldehyde-3-phosphatase, disrupting cellular glycolysis and eventually resulting in cell death 16,17 . Intra-articular injection of MIA causes chondrocyte cell death, leading to cartilage degeneration and subsequent subchondral bone alterations such as appearance of bone osteophytes 18,19 .…”

Section: Introductionmentioning

confidence: 99%

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse

Pitcher

Valente

Malcangio

2016

JoVE

108

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A major symptom of patients with osteoarthritis (OA) is pain that is triggered by peripheral as well as central changes within the pain pathways. The current treatments for OA pain such as NSAIDS or opiates are neither sufficiently effective nor devoid of detrimental side effects. Animal models of OA are being developed to improve our understanding of OA-related pain mechanisms and define novel pharmacological targets for therapy. Currently available models of OA in rodents include surgical and chemical interventions into one knee joint. The monoiodoacetate (MIA) model has become a standard for modelling joint disruption in OA in both rats and mice. The model, which is easier to perform in the rat, involves injection of MIA into a knee joint that induces rapid pain-like responses in the ipsilateral limb, the level of which can be controlled by injection of different doses. Intra-articular injection of MIA disrupts chondrocyte glycolysis by inhibiting glyceraldehyde-3-phosphatase dehydrogenase and results in chondrocyte death, neovascularization, subchondral bone necrosis and collapse, as well as inflammation. The morphological changes of the articular cartilage and bone disruption are reflective of some aspects of patient pathology. Along with joint damage, MIA injection induces referred mechanical sensitivity in the ipsilateral hind paw and weight bearing deficits that are measurable and quantifiable. These behavioral changes resemble some of the symptoms reported by the patient population, thereby validating the MIA injection in the knee as a useful and relevant pre-clinical model of OA pain.The aim of this article is to describe the methodology of intra-articular injections of MIA and the behavioral recordings of the associated development of hypersensitivity with a mind to highlight the necessary steps to give consistent and reliable recordings.

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Mono‐iodoacetate‐induced experimental osteoarthritis. A dose‐response study of loss of mobility, morphology, and biochemistry

Cited by 357 publications

References 26 publications

A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models

A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models

Radiographic and Histopathologic Analysis on Osteoarthritis Rat Model Treated with Essential Oils of Rosmarinus officinalis and Populus alba

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse

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