Meniscal biomechanical alterations in an ACLT rabbit model of early osteoarthritis

Levillain, Aurélie; Boulocher, C.; Kaderli, S.; Viguier, É.; Hannouche, Didier; Hoc, Thierry; Magoariec, Hélène

doi:10.1016/j.joca.2015.02.022

Cited by 27 publications

(29 citation statements)

References 43 publications

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“…Similar to articular cartilage, mechanical injuries can also alter the meniscus biomechanical properties, cause disorganisation of collagen network, tissue calcification and concomitant changes in GAG and collagen content (Katsuragawa et al , 2010; Kwok et al , 2014; Pauli et al , 2011; Sun et al , 2012). It was found that the changes in meniscus mechanical properties accompanied changes in the articular cartilage post ACLT; a significant loss (by almost a factor of two) of equilibrium and dynamic compressive stiffness in meniscus from the ACLT knee was observed at week 9, which is consistent with previous studies (Levillain et al , 2015). However, articular cartilage stiffness was significantly reduced at the earlier time point of 3 weeks post ACLT.…”

Section: Discussionsupporting

confidence: 91%

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: Discussionsupporting

confidence: 91%

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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“…Inflammation has been shown to have a catabolic effect on meniscal GAG coverage . The relationship between GAG coverage and modulus is not fully understood, but some studies have suggested that GAG coverage is related to equilibrium modulus while others report no such relationship . In the current study, there was a similar decline noted between GAG coverage and equilibrium modulus in both models based on the injured versus control limbs.…”

Section: Discussionsupporting

confidence: 65%

Comparison of two models of post‐traumatic osteoarthritis; temporal degradation of articular cartilage and menisci

Fischenich

Button

DeCamp

et al. 2016

Journal Orthopaedic Research

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The objective of this study was to compare longitudinal results from two models of combined anterior cruciate ligament (ACL) and meniscal injury. A modified ACL transection (mACLT) model and a traumatic impact (ACLF) model were used to create an ACL rupture and acute meniscal damage in a Flemish Giant animal model. The animals were euthanized at time points of 4, 8, or 12 weeks. The menisci were assessed for equilibrium and instantaneous compressive modulus, as well as glycosaminoglycan (GAG) coverage. The articular cartilage was mechanically assessed for thickness, matrix modulus, fiber modulus, and permeability. Articular cartilage GAG coverage, fissuring, tidemark integrity, and subchondral bone thickness were measured. Both models resulted in damage indicative of osteoarthritis, including decreased meniscal mechanics and GAG coverage, increased permeability and fissuring of articular cartilage, and decreased GAG coverage. The mACLT model had an early and lasting effect on the menisci mechanics and GAG coverage, while cartilage damage was not significantly affected until 12 weeks. The ACLF model resulted in an earlier change of articular cartilage GAG coverage and fissuring in both the 8 and 12 week groups. The menisci were only significantly affected at the 12 week time point in the ACLF model. We concluded the progression of post traumatic osteoarthritis was dependent on injury modality: a point to be considered in future investigations. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:486-495, 2017.

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“…Information of elastin fibers could hardly be collected from such images. A previous study showed a similar conclusion that elastin fibers were not detected in rabbit menisci and the signal of elastin was absent [19].…”

Section: Histological Analysis Of the Meniscisupporting

confidence: 52%

“…A multiphoton laser scanning microscope (FV1000MPE, Olympus, Japan) was used for observing the collagen microstructure. The excitation wavelength was set 850 nm [19], and two band pass filters (i.e., 420-460 nm and 495-540 nm) were used to acquire the second harmonic generation (SHG) from collagen and the two-photon excited fluorescence(TPEF) from cells and elastin. A 25X, 1.05 NA water immersion objective was used, and the image field was 508 × 508 µm 2 .…”

Section: Histological Analysismentioning

confidence: 99%

The collagen microstructural changes of rat menisci and tibiofemoral cartilages under the influence of mechanical loading: An in vitro wear test of whole joints

Cai

Hao

Xiao

et al. 2017

THC

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Abstract. BACKGROUND: Knee osteoarthritis (OA) is suggested to be induced by multi-factors, and mechanical environment is regarded as a risky factor. OBJECTIVE: To investigate the effect of isolated mechanical factor on cartilage. METHODS: An active wear test system was designed to perform parameters-controlled in vitro wear tests on rat knee joints with specific load magnitude, flexion-extension angle, and movement frequency. Six hind limbs of 9-month-old male SpragueDawley rats, with an additional spring on the medial side, were worn by using the custom-designed apparatus. Researchers observed both the menisci and tibial cartilages of these hind limbs using multiphoton laser scanning microscopy to analyze the change of the collagen microstructure caused by wear. RESULTS: Collagen microstructure of both the medial and lateral meniscus became disordered under cyclic load. Some tissues on the surface of the medial tibial cartilage were removed and the middle layer of the medial compartment displayed cracks. On the contrary, the lateral tibial cartilage was intact. CONCLUSIONS: The results implied that cyclic load caused menisci microstructure disarrangement prior to tibial cartilage damage and the collagen structure of mid-layer tibial cartilage failed before that of the superficial layer under the kinematics adopted in the study.

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Meniscal biomechanical alterations in an ACLT rabbit model of early osteoarthritis

Cited by 27 publications

References 43 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

Comparison of two models of post‐traumatic osteoarthritis; temporal degradation of articular cartilage and menisci

The collagen microstructural changes of rat menisci and tibiofemoral cartilages under the influence of mechanical loading: An in vitro wear test of whole joints

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