Alterations in subchondral bone plate, trabecular bone and articular cartilage properties of rabbit femoral condyles at 4 weeks after anterior cruciate ligament transection

Florea, Cristina; Malo, Markus; Rautiainen, Jari; Mäkelä, Janne; Fick, James M.; Nieminen, Miika T.; Jurvelin, Jukka S.; Davidescu, Arjana; Korhonen, Rami K.

doi:10.1016/j.joca.2014.11.023

Cited by 53 publications

(74 citation statements)

References 47 publications

(51 reference statements)

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“…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).…”

Section: Resultssupporting

confidence: 91%

“…Therefore, it was not possible to assess the effect of Dex or Av-Dex on these parameters. Abnormal joint loading (due to ACLT in this model) can lead to an adaptive bone remodelling process, decreasing trabecular bone volume fraction and thickness, due to an imbalance in bone resorption and formation in the more unloaded joint compartments (Florea et al , 2015). Finally, it was found that avidin penetrated through the complete thickness of articular cartilage and was retained within the tissue until at least 3 weeks (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The following measurements were obtained: volumetric trabecular bone mineral density [BMD; mg HA/cm 3 ], trabecular bone volume fraction (bone volume/total volume; BV/TV), trabecular number (Tb.N), mean thickness (Tb.Th; mm), mean separation (Tb. sp; mm), structural model index (SMI), quantifying the trabecular bone structure as either more rod- or plate-like (SMI values range from 0 for a perfect plate to 3 for a perfect rod, where negative values indicate concave trabecular surfaces) (Florea et al , 2015), and degree of anisotropy (DA), as an indicator of how the trabecular bone structural elements are oriented (Bouxsein et al , 2010). …”

Section: Methodsmentioning

confidence: 99%

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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: 91%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…Cartilage-onbone samples were harvested and biomechanical measurements were conducted on the medial (med) and lateral (lat) femoral condyles and tibial plateaus in the center of the weight-bearing areas and on the femoral groove in the center of the contact area with the patella for the knee in its neutrally flexed position (Julkunen et al, 2009a;Makela et al, 2014;Wei et al, 1998) (Fig. 1, see more details from Makela et al (2014) and Florea et al (2014) where the same samples were used). There were no significant differences (p 40.05) in sample thicknesses between ACLT, C-L and CTRL groups.…”

Section: Samples and Processingmentioning

confidence: 99%

Very early osteoarthritis changes sensitively fluid flow properties of articular cartilage

Mäkelä

Han

Herzog

et al. 2015

Journal of Biomechanics

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In this study, fibril-reinforced poroelastic (FRPE) modeling was used for rabbit knee after anterior cruciate ligament transection (ACLT) to assess how the mechanical properties of collagen, proteoglycans, and fluid in articular cartilage change in early osteoarthritis, and how site-specific these changes are. Unilateral ACLT was performed in eight skeletally mature, female New Zealand white rabbits. A separate control (CTRL) group consisted of knee joints of five non-operated rabbits. Animals were sacrificed at four weeks after ACLT and cartilage-on-bone samples from femoral groove, medial and lateral femoral condyles, and tibial plateaus were harvested. A stress-relaxation protocol in indentation geometry was applied and the FRPE model was fitted to the experimental force-time curve by minimizing the mean absolute error between experiment and simulation. The optimized parameters were: fibril network modulus (Ef), representing the collagen network; non-fibrillar matrix modulus (Enf), representing the PG matrix; and permeability (k), representing fluid flow. Permeability was increased significantly in the ACLT group compared to the CTRL group knees at all sites except for the medial tibial plateau. ACLT also caused a decrease in the Ef at all sites except for the medial and lateral tibial plateaus. The Enf of the ACLT group knees was altered only for the lateral femoral condyle. The results of this study suggest that early osteoarthritis primarily affects cartilage permeability and impairs the collagen network stiffness in a site-specific manner. These findings from early osteoarthritis indicate that fluid flow velocity in articular cartilage may change prior to quantifiable structural alterations in the tissue.

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“…Volumetric shapes include strips (Batiste et al, 2004), cylinders (Boudenot et al, 2014; Iijima et al, 2015; Intema et al, 2010; McErlain et al, 2008; Sniekers et al, 2008), and cubes (Florea et al, 2015). Sizes vary from small 2 x 2 x 4mm 3 cubes (Florea et al, 2015) to large anatomical contours that include the medial or lateral compartments of the tibia (Hamann et al, 2012; Maerz et al, 2016; Mohan et al, 2016). ROI location and number varies from a single load bearing location (Batiste et al, 2004; Boudenot et al, 2014) to multiple locations throughout the compartment (McErlain et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Comparison of micro-CT post-processing methods for evaluating the trabecular bone volume fraction in a rat ACL-transection model

Chin

Karamchedu

Patel

et al. 2016

Journal of Biomechanics

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Trabecular bone volume fraction assessments are likely sensitive to the analysis method and selection of the region of interest. Currently, there are several methods for selecting the region of interest to analyze trabecular bone in animal models of post-traumatic osteoarthritis. The objective of this study was to compare three published methods for determining the trabecular bone volume fraction of the medial tibial epiphyses in ACL transected and contralateral ACL intact knees. Micro-computed tomography images of both knees were obtained five weeks postoperatively and evaluated using three methods: (1) the Whole Compartment Method that captured the entire medial compartment, (2) the centrally located Single Core Method, and (3) the Triplet Core Method that averaged focal locations in the anterior, central, and posterior regions. The Whole Compartment method detected significant bone loss in the ACL transected knee compared to the ACL intact knee (p<0.001), with a loss of 15.2±3.9%. The Single Core and the Triplet Core Methods detected losses of 7.5±10.5% (p=0.061) and 14.1±13.7%(p=0.01), respectively. Details regarding segmentation methods are important for facilitating comparisons between studies, and for selecting methods to document trabecular bone changes and treatment outcomes. Based on these findings, the Whole Compartment Method is recommended, as it was least variable and more sensitive for detecting differences in the bone volume fraction in the medial compartment.

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Alterations in subchondral bone plate, trabecular bone and articular cartilage properties of rabbit femoral condyles at 4 weeks after anterior cruciate ligament transection

Cited by 53 publications

References 47 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

Very early osteoarthritis changes sensitively fluid flow properties of articular cartilage

Comparison of micro-CT post-processing methods for evaluating the trabecular bone volume fraction in a rat ACL-transection model

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