Use of routine clinical multimodality imaging in a rabbit model of osteoarthritis – part I

Bouchgua, M.; Alexander, Kate; d’Anjou, Marc-André; Girard, Christiane; Carmel, Éric Norman; Beauchamp, Guy; Richard, Hélène

doi:10.1016/j.joca.2008.06.017

Cited by 25 publications

(30 citation statements)

References 39 publications

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“…5g) and severity scores (Fig. 5h), in agreement with previous findings (Batiste et al , 2004; Bouchgua et al , 2009b; Bouchgua et al , 2009a). Treatment with Dex or avidin alone did not improve osteophyte volume or severity scores.…”

Section: Resultssupporting

confidence: 92%

Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis

Bajpayee¹,

Vega²,

Scheu³

et al. 2017

eCM

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Disease-modifying osteoarthritis drugs (DMOADs) should reach their intra-tissue target sites at optimal doses for clinical efficacy. The dense, negatively charged matrix of cartilage poses a major hindrance to the transport of potential therapeutics. In this work, electrostatic interactions were utilised to overcome this challenge and enable higher uptake, full-thickness penetration and enhanced retention of dexamethasone (Dex) inside rabbit cartilage. This was accomplished by using the positively charged glycoprotein avidin as nanocarrier, conjugated to Dex by releasable linkers. Therapeutic effects of a single intra-articular injection of low dose avidin-Dex (0.5 mg Dex) were evaluated in rabbits 3 weeks after anterior cruciate ligament transection (ACLT). Immunostaining confirmed that avidin penetrated the full cartilage thickness and was retained for at least 3 weeks. Avidin-Dex suppressed injury-induced joint swelling and catabolic gene expression to a greater extent than free Dex. It also significantly improved the histological score of cell infiltration and morphogenesis within the periarticular synovium. Micro-computed tomography confirmed the reduced incidence and volume of osteophytes following avidin-Dex treatment. However, neither treatment restored the loss of cartilage stiffness following ACLT, suggesting the need for a combinational therapy with a pro-anabolic factor for enhancing matrix biosynthesis. The avidin dose used caused significant glycosaminoglycan (GAG) loss, suggesting the use of higher Dex : avidin ratios in future formulations, such that the delivered avidin dose could be much less than that shown to affect GAGs. This charge-based delivery system converted cartilage into a drug depot that could also be employed for delivery to nearby synovium, menisci and ligaments, enabling clinical translation of a variety of DMOADs.

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Section: Resultssupporting

confidence: 92%

Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis

Bajpayee¹,

Vega²,

Scheu³

et al. 2017

eCM

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“…Dogs, goats, and horses can be imaged effectively using 1.5 and 3T clinical magnets with routine coils and sequencing [92, 93, 103, 107, 108]. Mice, rabbits, and guinea pigs are too small to undergo routine MRI in vivo [18, 24, 25, 109], and only recently has the feasibility of micro-MRI been demonstrated in rats [110]. …”

Section: Factors In Determining An Appropriate Animal Modelmentioning

confidence: 99%

“…A major problem in using the rabbit model is rabbit articular cartilage that is capable of regeneration, which may be due to the fact that rabbits up to 8 months of age can have open physes on growth plates in the distal femur and proximal tibia [123, 124]. Rabbit models of OA include ACL tear, [18, 19] meniscectomy [20] and chemically induced [21, 22]. Similar to mice and rats, postoperative management is difficult.…”

Section: Rabbitmentioning

confidence: 99%

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A Review of Translational Animal Models for Knee Osteoarthritis

et al. 2012

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Knee osteoarthritis remains a tremendous public health concern, both in terms of health-related quality of life and financial burden of disease. Translational research is a critical step towards understanding and mitigating the long-term effects of this disease process. Animal models provide practical and clinically relevant ways to study both the natural history and response to treatment of knee osteoarthritis. Many factors including size, cost, and method of inducing osteoarthritis are important considerations for choosing an appropriate animal model. Smaller animals are useful because of their ease of use and cost, while larger animals are advantageous because of their anatomical similarity to humans. This evidence-based review will compare and contrast several different animal models for knee osteoarthritis. Our goal is to inform the clinician about current research models, in order to facilitate the transfer of knowledge from the “bench” to the “bedside.”

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“…Assessment of bone quality in OA using MRI [11,13,18–20] and quantitative micro-computed tomography (µCT) of bone [21–23] has also revealed much information about ultra-structural bone density parameters and microarchitecture [24]. …”

Section: Introductionmentioning

confidence: 99%

Imaging longitudinal changes in articular cartilage and bone following doxycycline treatment in a rabbit anterior cruciate ligament transection model of osteoarthritis

Pinney¹,

Taylor²,

Doan³

et al. 2012

Magnetic Resonance Imaging

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Objective The development of osteoarthritis following traumatic anterior cruciate ligament (ACL) injury is well established. However, few reliable indicators of early osteoarthritic changes have been established, which has limited the development of effective therapies. T1ρ and T2 mapping techniques have the ability to provide highly accurate and quantitative measurements of articular cartilage degeneration in vivo. Relating these cartilaginous changes to high-resolution bone-densitometric evaluations of the late-stage osteoarthritic bone is crucial in elucidating the mechanisms of development of traumatic osteoarthritis (OA) and potential therapies for early- or late-stage intervention. Methods Twelve rabbits were monitored with in vivo magnetic resonance imaging (MRI) scans following ACL transection surgery with a contralateral leg sham operation. Six of the rabbits were treated with oral doxycycline for the duration of the experiment. At 12 weeks, the excised knees from three animals from each group (n=6 overall) were subjected to micro-computed tomography (CT) analysis. Results Consistent with previous studies, initial elevations in T1ρ and T2 values in ACL-transected animals were observed with relative normalization towards values see in sham-operated legs over the 12-week study. This biphasic pattern could hold diagnostic potential to differentiate osteoarthritic cartilage by tracking the relative proportions of T1ρ and T2 values as they rise with inflammation then fall as collagen and proteoglycan loss leads to further dehydration. The addition of doxycycline resulted in inconclusive, yet potentially interesting, cartilaginous changes in several compartments of the rabbit legs. Micro-CT studies demonstrated decreased bone densitometrics in ACL-transected knees. Correlation studies suggest that the cartilaginous changes may be associated with some aspects of bony change and the development of OA. Conclusion We conclude that there are definite relationships between cartilaginous changes as seen on MRI and late-stage microstructural bony changes after traumatic ACL injury in rabbits. In addition, doxycycline may show promise in mitigating early-stage cartilage damage that may serve to lessen late-stage osteoarthritic changes. This study demonstrates the ability to track OA progression and therapeutic efficacy with imaging modalities in vivo.

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Use of routine clinical multimodality imaging in a rabbit model of osteoarthritis – part I

Cited by 25 publications

References 39 publications

Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis

Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis

A Review of Translational Animal Models for Knee Osteoarthritis

Imaging longitudinal changes in articular cartilage and bone following doxycycline treatment in a rabbit anterior cruciate ligament transection model of osteoarthritis

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