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

Abstract

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.

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

“…These trends became statistically significant by week 9. Similar trends are reported in earlier studies (Bouchgua et al , 2009b; Florea et al , 2015; Pinney et al , 2012; Wang et al , 2007). Treatment with Dex did not restore bone volume fraction, but with Av-Dex, the difference in BV/TV between ACLT and control groups was no longer statistically significant (Table 3b).…”

Kartogenin treatment prevented joint degeneration in a rodent model of osteoarthritis: A pilot study

“…Cartilage matrix degradation is a characteristic feature of OA and compositional MRI can assess early biochemical (proteoglycan and collagen content) and structural changes in the cartilage. Quantitative MRI techniques such as T 1ρ and T 2 were shown to provide quantitative measurements of articular cartilage degeneration . MR imaging of OA animal models enable detection of early pathological changes, track disease progression and test suitable drugs for OA.…”

Monitoring Cartilage Tissue Engineering Using Magnetic Resonance Spectroscopy, Imaging, and Elastography

“…124 MRI is currently used to study the cartilage regeneration and restoration in animal models and in human patients, and there have been attempts to incorporate MRS information as well. [125][126][127] In vivo studies using bioreactors (incubators) and animal models are important for validating new approaches of tissue engineering. MR compatible bioreactors allow the investigator to continuously monitor tissue regeneration over a period of days to weeks, which is important for optimizing growth conditions and viewing developing tissue structures.…”