Angiogenic activity of subchondral bone during the progression of osteoarthritis in a rabbit anterior cruciate ligament transection model

Saito, M.; Sasho, Takahisa; Yamaguchi, Satoshi; Ikegawa, N.; Akagi, Ryuichiro; Muramatsu, Yusuke; Mukoyama, S.; Ochiai, Nobuyasu; Nakamura, Junichi; Nakagawa, Kōichi; Nakajima, Aya; Takahashi, Kazuhisa

doi:10.1016/j.joca.2012.08.023

Cited by 34 publications

(36 citation statements)

References 35 publications

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“…Because the biomechanical instability (due to ACLT) is not corrected in this model, it was decided to focus on early degenerative changes that could be prevented by a single, early injection of Dex: this approach modelled the critical clinical window between an ACL tear and arthroscopic repair. However, less degenerative changes were observed macroscopically in the lateral femoral condyle cartilage than in the medial femoral condyles at 3 weeks post-ACLT, in agreement with previous observations made in this rabbit model (Le Graverand et al , 2002; Saito et al , 2012). Because only lateral condyles were used for histology, this reduced the ability to ascertain treatment effects on cartilage degeneration by histological scoring.…”

Section: Discussionsupporting

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: Discussionsupporting

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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“…In a longer study investigating tibial plateau changes, Issac et al (Isaac et al, 2010b) reported significant increases in fissuring and loss of GAG at 6 and 12 months. While not all of these models included ACL failure, outcomes from this impact-induced ACL failure model are in agreement with these previous studies (Saito et al, 2012; Makoto Yoshioka et al, 1996). Significant loss of GAG and an increase of surface fissuring were documented in the medial femur.…”

Section: Discussionsupporting

confidence: 89%

Chronic changes in the articular cartilage and meniscus following traumatic impact to the lapine knee

Fischenich

Button

Coatney

et al. 2015

Journal of Biomechanics

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The objective of this study was to induce anterior cruciate ligament (ACL) and meniscal damage, via a single tibiofemoral compressive impact, in order to document articular cartilage and meniscal changes post impact. Tibiofemoral joints of Flemish Giant rabbits were subjected to a single blunt impact that ruptured the ACL and produced acute meniscal damage. Animals were allowed unrestricted cage activity for 12 weeks before euthanasia. India ink analysis of the articular cartilage revealed higher degrees of surface damage on the impacted tibias (p=0.018) and femurs (p<0.0001) compared to controls. Chronic meniscal damage was most prevalent in the medial central and medial posterior regions. Mechanical tests revealed an overall 19.4% increase in tibial plateau cartilage thickness (p=0.026), 34.8% increase in tibial plateau permeability (p=0.054), 40.8% increase in femoral condyle permeability (p=0.029), and 20.1% decrease in femoral condyle matrix modulus (p=0.012) in impacted joints compared to controls. Both the instantaneous and equilibrium moduli of the lateral and medial menisci were decreased compared to control (p<0.02). Histological analyses revealed significantly increased presence of fissures in the medial femur (p = 0.036). In both the meniscus and cartilage there was a significant decrease in GAG coverage for the impacted limbs. Based on these results it is clear that an unattended combined meniscal and ACL injury results in significant changes to the soft tissues in this experimental joint 12 weeks post injury. Such changes are consistent with a clinical description of mid to late stage PTOA of the knee.

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“…So, osteoarthritis is considered an OC disease and possibly bone dependent because of the inflammatory factors delivered by the vasculature present in the subchondral bone . Blood vessels from the subchondral bone invade the articular cartilage promoting the progression of osteoarthritis and forming osteophytes . However, hyaline healthy cartilage is avascular while subchondral bone is vascular.…”

Section: Discussionmentioning

confidence: 97%

Biochemical Gradients to Generate 3D Heterotypic‐Like Tissues with Isotropic and Anisotropic Architectures

Canadas

Ren

Marques

et al. 2018

Adv Funct Materials

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Anisotropic 3D tissue interfaces with functional gradients found in nature are replicated in vitro for drug development and tissue engineering. Even though different fabrication techniques, based on material science engineering and microfluidics, are used to generate such microenvironments, mimicking the native tissue gradient is still a challenge. Here, the fabrication of 3D structures are described with linear/random porosity and gradient distribution of hydroxyapatite microparticles which are combined with a gradient of growth factors generated by a dual chamber for the development of heterotypiclike tissues. The hydroxyapatite gradient is formed by applying a thermal ramp from the first to the second gel layer, and the porous architecture is controlled through ice templating. A 3D osteochondral (OC) tissue model is developed by codifferentiating fat pad adipose-derived stem cells. Osteogenic and chondrogenic markers expression is spatially controlled, as it occurs in the native osteochondral unit. Additionally, a prevasculature is spatially induced by the perfusion of proangiogenic medium in the bone-like region, as observed in the native subchondral bone. Thus, in this study, precise spatial control is developed over cell/tissue phenotype and formation of prevasculature which opens up possibilities for the study of complex tissues interfaces, with broader applications in drug testing and regenerative medicine.

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Angiogenic activity of subchondral bone during the progression of osteoarthritis in a rabbit anterior cruciate ligament transection model

Abstract: Angiogenic activity of subchondral bone was elevated in the early to progressive stage of OA and vascular invasion into the osteochondral junction followed.

Cited by 34 publications

References 35 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

Chronic changes in the articular cartilage and meniscus following traumatic impact to the lapine knee

Biochemical Gradients to Generate 3D Heterotypic‐Like Tissues with Isotropic and Anisotropic Architectures

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