177,210 research outputs found

    Tenascin-C fragments are endogenous inducers of cartilage matrix degradation

    Get PDF
    Cartilage destruction is a hallmark of osteoarthritis (OA) and is characterized by increased protease activity resulting in the degradation of critical extracellular matrix (ECM) proteins essential for maintaining cartilage integrity. Tenascin-C (TN-C) is an ECM glycoprotein, and its expression is upregulated in OA cartilage. We aimed to investigate the presence of TN-C fragments in arthritic cartilage and establish whether they promote cartilage degradation. Expression of TN-C and its fragments was evaluated in cartilage from subjects undergoing joint replacement surgery for OA and RA compared with normal subjects by western blotting. The localization of TN-C in arthritic cartilage was also established by immunohistochemistry. Recombinant TN-C fragments were then tested to evaluate which regions of TN-C are responsible for cartilage-degrading activity in an ex vivo cartilage explant assay measuring glycosaminoglycan (GAG) release, aggrecanase and matrix metalloproteinase (MMP) activity. We found that specific TN-C fragments are highly upregulated in arthritic cartilage. Recombinant TN-C fragments containing the same regions as those identified from OA cartilage mediate cartilage degradation by the induction of aggrecanase activity. TN-C fragments mapping to the EGF-L and FN type III domains 3-8 of TN-C had the highest levels of aggrecan-degrading ability that was not observed either with full-length TN-C or with other domains of TN-C. TN-C fragments represent a novel mechanism for cartilage degradation in arthritis and may present new therapeutic targets for the inhibition of cartilage degradation

    Use of autologous adipose-derived mesenchymal stem cells for creation of laryngeal cartilage

    Get PDF
    OBJECTIVES/HYPOTHESIS: Adipose-derived mesenchymal stem cells (ASCs) are an exciting potential cell source for tissue engineering because cells can be derived from the simple excision of autologous fat. This study introduces a novel approach for tissue-engineering cartilage from ASCs and a customized collagen oligomer solution, and demonstrates that the resultant cartilage can be used for laryngeal cartilage reconstruction in an animal model. STUDY DESIGN: Basic science experimental design. METHODS: ASCs were isolated from F344 rats, seeded in a customized collagen matrix, and cultured in chondrogenic differentiation medium for 1, 2, and 4 weeks until demonstrating cartilage-like characteristics in vitro. Large laryngeal cartilage defects were created in the F344 rat model, with the engineered cartilage used to replace the cartilage defects, and the rats followed for 1 to 3 months. Staining examined cellular morphology and cartilage-specific features. RESULTS: In vitro histological staining revealed rounded chondrocyte-appearing cells evenly residing throughout the customized collagen scaffold, with positive staining for cartilage-specific markers. The cartilage was used to successfully repair large cartilaginous defects in the rat model, with excellent functional results. CONCLUSIONS: This study is the first study to demonstrate, in an animal model, that ASCs cultured in a unique form of collagen oligomer can create functional cartilage-like grafts that can be successfully used for partial laryngeal cartilage replacement

    Dickkopf-3 is upregulated in osteoarthritis and has a chondroprotective role

    Get PDF
    Objective Dickkopf-3 (Dkk3) is a non-canonical member of the Dkk family of Wnt antagonists and its upregulation has been reported in microarray analysis of cartilage from mouse models of osteoarthritis (OA). In this study we assessed Dkk3 expression in human OA cartilage to ascertain its potential role in chondrocyte signaling and cartilage maintenance. Methods Dkk3 expression was analysed in human adult OA cartilage and synovial tissues and during chondrogenesis of ATDC5 and human mesenchymal stem cells. The role of Dkk3 in cartilage maintenance was analysed by incubation of bovine and human cartilage explants with interleukin-1 (IL1) and oncostatin-M (OSM). Dkk3 expression was measured in cartilage following murine hip avulsion. Whether Dkk3 influenced Wnt, TGF and activin cell signaling was assessed in primary human chondrocytes and SW1353 chondrosarcoma cells using RT-qPCR and luminescence assays. Results Increased gene and protein levels of Dkk3 were detected in human OA cartilage, synovial tissue and synovial fluid. DKK3 expression was decreased during chondrogenesis of both ATDC5 cells and humans MSCs. Dkk3 inhibited IL1 and OSM-mediated proteoglycan loss from human and bovine cartilage explants and collagen loss from bovine cartilage explans. Cartilage DKK3 expression was decreased following hip avulsion injury. TGF signaling was enhanced by Dkk3 and Wnt3a and activin signaling were inhibited. Conclusions We provide evidence that Dkk3 is upregulated in OA and may have a protective effect on cartilage integrity by preventing proteoglycan loss and helping to restore OA-relevant signaling pathway activity. Targeting Dkk3 may be a novel approach in the treatment of OA

    Histological Analysis of Failed Cartilage Repair after Marrow Stimulation for the Treatment of Large Cartilage Defect in Medial Compartmental Osteoarthritis of the Knee

    Get PDF
    Bone marrow-stimulating techniques such as microfracture and subchondral drilling are valuable treatments for full-thickness cartilage defects. However, marrow stimulation-derived reparative tissues are not histologically well-documented in human osteoarthritis. We retrospectively investigated cartilage repairs after marrow stimulation for the treatment of large cartilage defects in osteoarthritic knees. Tissues were obtained from patients who underwent total knee arthroplasty (TKA) after arthroscopic marrow stimulation in medial compartmental osteoarthritis. Clinical findings and cartilage repair were assessed. Sections of medial femoral condyles were histologically investigated by safranin O staining and anti-type II collagen antibody. Marrow stimulation decreased the knee pain in the short term. However, varus leg alignment gradually progressed, and TKA conversions were required. The grade of cartilage repair was not improved. Marrow stimulations resulted in insufficient cartilage regeneration on medial femoral condyles. Safranin O-stained proteoglycans and type II collagen were observed in the deep zone of marrow-stimulated holes. This study demonstrated that marrow stimulation resulted in failed cartilage repair for the treatment of large cartilage defects in osteoarthritic knees. Our results suggest that arthroscopic marrow stimulation might not improve clinical symptoms for the long term in patients suffering large osteoarthritic cartilage defects

    Imaging of nuclear magnetic resonance spin–lattice relaxation activation energy in cartilage

    Get PDF
    Samples of human and bovine cartilage have been examined using magnetic resonance imaging to determine the proton nuclear magnetic resonance spin–lattice relaxation time, T1, as a function of depth within through the cartilage tissue. T1 was measured at five to seven temperatures between 8 and 38°C. From this, it is shown that the T1 relaxation time is well described by Arrhenius-type behaviour and the activation energy of the relaxation process is quantified. The activation energy within the cartilage is approximately 11 ± 2 kJ mol−1 with this notably being less than that for both pure water (16.6 ± 0.4 kJ mol−1) and the phosphate-buffered solution in which the cartilage was immersed (14.7 ± 1.0 kJ mol−1). It is shown that this activation energy increases as a function of depth in the cartilage. It is known that cartilage composition varies with depth, and hence, these results have been interpreted in terms of the structure within the cartilage tissue and the association of the water with the macromolecular constituents of the cartilage

    Acute Effects of Walking on The Deformation of Femoral Articular Cartilage

    Full text link
    Background and Purpose: Knee osteoarthritis (OA) is characterized by a progressive loss of the articular cartilage, increasing the amount of friction in the joint, resulting in pain and decreases in mobility and function. Additionally, it has been demonstrated that frontal plane lower extremity (LE) malalignment (e.g., varus, valgus) is associated with onset and progression of OA. Previous studies showed that static loading of 50% body weight at the knee results in more cartilage deformation in those with knee OA compared to healthy controls. As walking produces forces in the knee that are 2-3 times body weight, it may result in greater cartilage deformation. The purpose of our study was to compare the acute effects of walking on the femoral cartilage deformation between individuals with and without knee OA and determine whether LE alignment is associated with greater cartilage deformation. Subjects: 10 subjects without OA (5 females and 5 males; 55.0 ± 1.8 yrs; 78.8 ± 14.0 kg; 1.8 ± 0.2 m) and 9 subjects with OA were recruited (4 females and 5 males; 55.6 ± 4.5 yrs; 97.4 ± 15.0 kg; 1.7 ± 0.1 m). Methods: Each subject underwent X-ray and MRI assessment. For X-ray assessment, persons with Kellgren/Lawrence grades 2-3 were assigned to the OA group whereas subjects with grades 0-1 were assigned to the control group. During MRI assessment, 3T, frontal-plane MRI was obtained before and immediately after 30 minutes of treadmill walking at 3-4 mph. LE alignment was obtained by measuring the angle between the long axes of femur and tibia using a goniometer. To obtain cartilage deformation post-walking, the medial and lateral femoral cartilage of the weight-bearing areas were segmented on subjects’ MRI. Cartilage thickness was quantified by computing the perpendicular distance between opposing voxels defining the edges of the femoral cartilage. Cartilage volume was quantified by multiplying the segmented area by slice thickness. Independent t-tests were used to compare cartilage deformation (i.e., percent changes in medial and lateral cartilage thickness/volume) in response to walking between the 2 groups. Pearson correlation coefficients were used to assess the association between cartilage deformation and LE alignment of all subjects. Results: Independent t-tests revealed no significant difference in percent change of cartilage thickness between OA group and control group in medial (p=0.873) or lateral (p=0.688) femur. Additionally, there was no difference in percent change of cartilage volume between the two groups in medial (p=0.159) or lateral (p=0.327) femur. Pearson correlation coefficient analyses revealed a significant correlation between reductions in lateral femoral cartilage thickness and increased knee valgus alignment (p=0.030)

    Cell sources for articular cartilage repair strategies: shifting from mono-cultures to co-cultures

    Get PDF
    The repair of articular cartilage is challenging due to the sparse native cell population combined with the avascular and aneural nature of the tissue. In recent years cartilage tissue engineering has shown great promise. As with all tissue engineering strategies, the possible therapeutic outcome is intimately linked with the used combination of cells, growth factors and biomaterials. However, the optimal combination has remained a controversial topic and no consensus has been reached. In consequence, much effort has been dedicated to further design, investigate and optimize cartilage repair strategies. Specifically, various research groups have performed intensive investigations attempting to identify the single most optimal cell source for articular cartilage repair strategies. However, recent findings indicate that not the heavily investigated mono cell source, but the less studied combinations of cell sources in co-culture might be more attractive for cartilage repair strategies. This review will give a comprehensive overview on the cell sources that have been investigated for articular cartilage repair strategies. In particular, the advantages and disadvantages of investigated cell sources are comprehensively discussed with emphasis on the potential of co-cultures in which benefits are combined while the disadvantages of single cell sources for cartilage repair are mitigated
    corecore