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ABSTRACT: Osteochondral lesions require treatment to restore the biology and functionality of the joint. A novel nanostructured biomimetic gradient scaffold was developed to mimic the biochemical and biophysical properties of the different layers of native osteochondral structure. The present results show that the scaffold presents important physicochemical characteristics and can support the growth and differentiation of mesenchymal stromal cells (h-MSCs), which adhere and penetrate into the cartilaginous and bony layers. H-MSCs grown in chondrogenic or osteogenic medium decreased their proliferation during days 14-52 on both scaffold layers and in medium without inducing factors used as controls. Both chondrogenic and osteogenic differentiation of h-MSCs occurred from day 28 and were increased on day 52, but not in the control medium. Safranin O staining and collagen type II and proteoglycans immunostaining confirmed that chondrogenic differentiation was specifically induced only in the cartilaginous layer. Conversely, von Kossa staining, osteocalcin and osteopontin immunostaining confirmed that osteogenic differentiation occurred on both layers. This study shows the specific potential of each layer of the biomimetic scaffold to induce chondrogenic or osteogenic differentiation of h-MSCs. These processes depended mainly on the media used but not the biomaterial itself, suggesting that the local milieu is fundamental for guiding cell differentiation. Copyright © 2013 John Wiley & Sons, Ltd.
Journal of Tissue Engineering and Regenerative Medicine 03/2013; · 3.28 Impact Factor
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ABSTRACT: Bone marrow is one of the best characterized stem cell microenvironments that contains Mesenchymal Stem Cells (MSCs), a rare population of non-hematopoietic stromal cells. MSCs have been indicated as a new option for regenerative medicine because of their ability to differentiate into various lineages such as bone, cartilage and adipose tissue. However, isolation procedures are crucial for the functional activity of the transplanted cells. The use of concentrated bone marrow cells (BMCs) enables a cell population surrounded by its microenvironment (niche) to be implanted while avoiding all the complications related to the in vitro culture. The cells of the niche are able to regulate stem cell behavior through direct physical contact and secreting paracrine factors. The aim of this study was to characterize BMCs in vitro to evaluate their ability to differentiate toward mature cells and try to understand whether there are differences in the chondrogenic and osteogenic potential of cells from patients of different ages. Mononuclear Cells (MNCs) isolated by Ficoll were used as control. Both cell populations were grown in monolayers and differentiated with specific factors and analyzed by histological and molecular biology assays to evaluate the expression of some specific extracellular matrix molecules. The present investigations revealed the ability of BMCs to act as isolated cells. They are able to form colonies and differentiate toward chondrogenic and osteogenic lineages, the latter pathway appearing to be influenced by donor age. The results obtained by this study support the use of BMCs in clinical practice for the repair of osteochondral damage, which might be particularly useful for the one-step procedure allowing cells to be directly implanted in operating room.
Journal of biological regulators and homeostatic agents 01/2013; 27(1):165-175. · 5.18 Impact Factor
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Arthritis Research & Therapy 04/2012; 3:1-1. · 4.45 Impact Factor
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ABSTRACT: Mesenchymal Stem Cells (MSCs) are a population of adherent cells that can differentiate into mesenchymal lineage populations (cartilage, bone and fat tissue). In addition, they seem to be able to differentiate also into a broader type of lineages other than the original mesodermal germ layer. Bone marrow MSCs are a standard in the field of adult stem cell biology and clinical applications; however adipose-derived MSCs are becoming an attractive alternative due to their minimally invasive accessibility and availability in the body. MSCs modulate several effector immune functions by interacting both with innate and adoptive immune responses. Several local signals from the tissue microenvironment, together with cytokine and soluble factors released by MSCs influence anti-inflammatory and tissue repair properties of infused MSCs. Therefore, cellular therapies utilizing ex vivo expanded MSCs may be an interesting approach for inflammatory and autoimmune diseases. Biosafety is still one of the most important aspects; therefore the production of clinical-grade MSCs requires the careful identification and control of all the phases of cell manipulation and release. Many clinical applications of adult MSCs are in progress and are using bone marrow or adipose tissue-derived MSCs for the treatment of Graft Versus Host Disease (GVHD), inflammatory joint diseases and osteocartilagineous defects, digestive tract, cardiovascular and neurological diseases.
Current pharmaceutical design 01/2012; 18(13):1821-45. · 4.41 Impact Factor
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ABSTRACT: Mutations in genes encoding nuclear envelope proteins, particularly LMNA encoding the A-type lamins, cause a broad range of diverse diseases, referred to as laminopathies. The astonishing variety of diseased phenotypes suggests that different mechanisms could be involved in the pathogenesis of laminopathies. In this review we will focus mainly on two of these pathogenic mechanisms: the nuclear damages affecting the chromatin organization, and the oxidative stress causing un-repairable DNA damages. Alteration in the nuclear profile and in chromatin organization, which are particularly impressive in systemic laminopathies whose cells undergo premature senescence, are mainly due to accumulation of unprocessed prelamin A. The toxic effect of these molecular species, which interfere with chromatin-associated proteins, transcription factors, and signaling pathways, could be reduced by drugs which reduce their farnesylation and/or stability. In particular, inhibitors of farnesyl transferase (FTIs), have been proved to be active in rescuing the altered cellular phenotype, and statins, also in association with other drugs, have been included into pilot clinical trials. The identification of a mechanism that accounts for accumulation of un-repairable DNA damage due to reactive oxygen species (ROS) generation in laminopathic cells, similar to that found in other muscular dystrophies (MDs) caused by altered expression of extracellular matrix (ECM) components, suggests that anti-oxidant therapeutic strategies might prove beneficial to laminopathic patients.
European journal of histochemistry: EJH 01/2012; 56(4):e45. · 1.69 Impact Factor
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ABSTRACT: Polyamines are naturally occurring, positively charged polycations which are able to control several cellular processes in different cell types, by interacting with negatively charged compounds and structures within the living cell. Functional genomics in rodents targeting key biosynthetic or catabolic enzymes have revealed a series of phenotypic changes, many of them related to human diseases. Several pieces of evidence from the literature point at a role of polyamines in promoting chondrocyte differentiation, a process which is physiological in growth plate maturation or fracture healing, but has pathological consequences in articular chondrocytes, programmed to keep a maturational arrested state. Inappropriate differentiation of articular chondrocytes results in osteoarthritis. Thus, we have studied the effects of exogenously added spermine or spermidine in chondrocyte maturation recapitulated in 3D cultures, to tease out the effects on gene and protein expression of key chondrogenesis regulatory transcription factors, markers and effectors, as well as their posttranscriptional regulation. The results indicate that both polyamines are able to increase the rate and the extent of chondrogenesis, with enhanced collagen 2 deposition and remodeling with downstream generation of collagen 2 bioactive peptides. These were able to promote nuclear localization of RUNX-2, the pivotal transcription factor in chondrocyte hypertrophy and osteoblast generation. Indeed, samples stimulated with polyamines showed an enhanced mineralization, along with increased caspase activity, indicating increased chondrocyte terminal differentiation. In conclusion these results indicate that the polyamine pathway can represent a potential target to control and correct chondrocyte inappropriate maturation in osteoarthritis.
Amino Acids 08/2011; 42(2-3):667-78. · 3.25 Impact Factor
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ABSTRACT: Recent studies have shown that aldosterone may play a critical role in the transition to heart failure and that heart is a direct target of the action of aldosterone, which can provoke hypertrophy and apoptosis of isolated cardiomyocytes and also increase the expression of genes that favor tissue fibrosis. Early work from this and other laboratories has established a link between the aliphatic polyamines and cardiac hypertrophy, while more recently an involvement of polyamines even in cell death and survival has emerged. In the present study we have treated cardiac cells, i.e. rat H9c2 cardiomyoblasts and neonatal cardiomyocytes, with (D, L)-2-(difluoromethyl)ornithine, a specific inhibitor of polyamine biosynthesis, to investigate the effects of polyamines in relation to the hypertrophic, pro-fibrotic and pro-apoptotic actions of aldosterone. The results indicate that inhibition of polyamine biosynthesis may prevent or attenuate the adverse actions of aldosterone, by modulating the expression of genes related to cardiac hypertrophy and fibrosis, as well as the levels of proteins and the activities of enzymes that control apoptosis.
Amino Acids 12/2009; 38(2):525-31. · 3.25 Impact Factor
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ABSTRACT: ABSTRACT— Six acute phase proteins (haptoglobin, α 1-acid glycoprotein, α 1-antitrypsin, α2-macroglobulin, C reactive protein and transferrin) have been measured in the sera of chronic liver disease (CLD) patients with different aetiology (viral, autoimmune and alcoholic) and histology (steatosis, chronic persistent hepatitis, chronic active hepatitis, cirrhosis), and in patients with liver cancer. 1) The most striking changes concerned α2-macroglobulin (increased) and haptoglobin (decreased) levels. 2) Transferrin was lower in alcoholic liver disease than in viral CLD, CRP was lower in autoimmune than in viral or alcoholic CLD, and α 1-acid glycoprotein was lower in viral and alcoholic CLD than in autoimmune CLD. Acute phase protein assay may prove useful in differential diagnosis, particularly when specific markers are not available (autoimmune, non A, non B, alcoholic liver diseases). 3) No significant differences related to aetiology (B, non A non B, D viruses) were observed in viral CLD. 4) Patients who progressed to CLD after acute viral hepatitis type B or non A non B did not show different APP levels from those who had recovered when tested 8–12 months after the acute phase. 5) The pattern of APP changes observed in primary liver cell carcinoma was different from both the cirrhotic pattern and the pattern presented by other tumours with or without liver metastasis.
Liver International 12/2008; 8(2):65 - 74.
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ABSTRACT: The anterior cruciate ligament (ACL) is the most commonly injured tissue of the human knee. Its poor ability to regenerate after injury represents a challenge to ligament tissue engineering. An understanding of the molecular composition of the structures used for its repair is essential for clinical assessments and for the implementation of tissue engineering strategies. The objective of this study was to evaluate, both at gene and protein levels, the expression of characteristic molecules in human ACL, patellar, semitendinosus and gracilis tendons and in the ligament reconstructed with patellar or semitendinosus and gracilis tendons. We demonstrated that primary ACL and tendon tissues all express collagen I, II, Sox-9, tenascin-C and aggrecan. Collagen X expression was detected at very low levels or undetectable. Cathepsin B, MMP-1 and MMP-13 were expressed at higher levels in the ACL reconstructed by the two tendons, showing that a remodeling process occurs during "ligamentization". Both our molecular and immunohistochemical evaluations did not reveal significative differences between the tendons and ligaments analyzed. However, ACL reconstructed with semitendinosus and gracilis tendon seems to present a higher expression of collagen type II when compared to that reconstructed with patellar tendon. This study could give a reasonable identification of genetic and protein markers specific to tendon/ligament tissues and be helpful in testing tissue engineering approaches for ACL reconstruction.
Journal of Biomedical Materials Research Part A 02/2008; 84(1):117-27. · 2.63 Impact Factor
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ABSTRACT: To investigate the gene expression profile and the histological aspects of articular cartilage of patients affected by Morquio syndrome, a lysosomal storage disease characterized by the accumulation of glycosaminoglycans within the cells which result in abnormal formation and growth of the skeletal system.
Articular cartilage samples were obtained from the femoral condyle of two siblings with Morquio syndrome during surgery performed to treat valgus knee. As controls, four biopsy samples of healthy cartilage were obtained from four different male multiorgan donors. A Real-Time Polymerase Chain reaction (RT-PCR) analysis was performed to evaluate the expression of type I and II collagens and aggrecan mRNAs. Histological and immunohistochemical analyses for some matrix proteins were carried out on paraffin embedded sections.
Type I collagen mRNA mean level was higher in the samples of patients with Morquio syndrome compared to controls. Type II collagen and aggrecan mRNAs' mean expression was instead lower. The morphological appearance of the cartilage showed a poorly organized tissue structure with not homogeneously distributed cells that were larger compared to normal chondrocytes due to the presence inside the vacuoles of proteoglycans which were not metabolized. Chondrocytes were negative for collagen II immunostaining while the extracellular matrix was weakly positive. Collagen type I immunostaining was positive at cellular level. Keratan sulfate showed diffuse positivity and chondroitin-6-sulfate was present throughout the cartilaginous thickness.
In cartilage of patients with Morquio syndrome, a low expression of collagen type II and a high expression of collagen type I both at protein and molecular levels are evidentiated. This finding could give evidence of the reduction in ankle and knee joint movement observable in these patients.
Osteoarthritis and Cartilage 12/2007; 15(11):1311-7. · 3.90 Impact Factor
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ABSTRACT: Growing evidence suggests a role for polyamines in apoptosis, although the relationship appears to be complex. alpha-Difluoromethylornithine (DFMO), a largely used ornithine decarboxylase inhibitor, is cytostatic, hardly cytotoxic and may even increase the resistance of tumour cells to some apoptotic stimuli. This may represent a problem in cancer therapy, where the killing of tumoral cells would be a desired effect, but could be an advantage in other pathological contexts related to an excess of apoptosis, such as cardiovascular diseases, stem cell transplantation, arthritis and infections. In different cellular models, polyamine depletion following treatment with polyamine biosynthesis inhibitors appears to inhibit mitochondrial and death receptor pathways of apoptosis by affecting key proteins. These studies indicate that inhibition of polyamine biosynthesis may prevent or reduce the apoptotic response triggered by a variety of stimuli in non-tumoral cells, such as cardiac cells, stem cells, chondrocytes, macrophages and intestinal epithelial cells.
Amino Acids 09/2007; 33(2):197-202. · 3.25 Impact Factor
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Histopathology 01/2007; 51(1):133-134. · 3.08 Impact Factor
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ABSTRACT: To test the importance of the interleukin-4 (IL-4)/IL-4 receptor (IL-4R) system in osteoarthritis (OA) we evaluated soluble IL-4R (sIL-4R) levels in sera of patients with different forms of OA and healthy individuals.
We recruited: 141 patients with hand OA, 70 with nodal and 71 with erosive hand OA; 64 patients undergoing total joint replacement, 34 with hip and 30 with knee OA; and 38 ethnically and geographically age-matched healthy individuals [normal controls (NC)].
Serum sIL-4R concentration was found to be significantly higher in all OA patients than that in NC. When patients were divided into four subgroups (nodal, erosive, hip and knee OA) significant differences were present when comparing NC with each subgroup. This was true also when small-joint OA groups were compared with large-joint OA groups, the latter being associated with higher IL-4R levels.
We found increased levels of sIL-4R in OA patients compared with healthy individuals. We speculate that this reduces availability of IL-4, and its effects on chondrocytes.
Osteoarthritis and Cartilage 08/2006; 14(7):717-9. · 3.90 Impact Factor
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ABSTRACT: Angiogenesis is a process stimulated in inflamed synovium of patients with osteoarthritis (OA), and contributes to the progression of the disease. Synovial fibroblasts secrete angiogenic factors, such as vascular endothelial growth factor (VEGF), an up-regulator of angiogenesis, and this ability is increased by interleukin (IL)-1beta. The purpose of this study was to verify whether IL-17 contributes and/or synergizes with IL-1beta and tumor necrosis factor (TNF)-alpha in vessel development in articular tissues by stimulating the secretion of proangiogenic factors by synovial fibroblasts.
We stimulated in vitro synovial fibroblasts isolated from OA, rheumatoid arthritis (RA) and fractured patients (FP) with IL-17 and IL-1beta and from OA patients with IL-17, IL-1beta and TNF-alpha. In the supernatants from the cultures, we assayed the amount of VEGF by immunoassay and other angiogenic factors (keratinocyte growth factor, KGF; hepatocyte growth factor, HGF; heparin-binding endothelial growth factor, HB-EGF; angiopoietin-2, Ang-2; platelet-derived growth factor B, PDGF-BB; thrombopoietin, TPO) by chemiluminescence; semiquantitative RT-PCR was used to state mRNA expression of nonreleased angiogenic factors (Ang-2 and PDGF-BB) and tissue inhibitors of metalloproteinase (TIMP)-1.
IL-17, TNF-alpha and IL-1beta increased VEGF secretion by synovial fibroblasts from OA patients. IL-17 and IL-1beta also increased VEGF secretion in RA and FP. Besides, IL-17 increased KGF and HGF secretions in OA, RA and FP; in OA and RA, IL-17 also increased the HB-EGF secretion and the expression of TIMP-1 as protein and mRNA. In OA patients IL-17 had an additive effect on TNF-alpha-stimulated VEGF secretion.
These results suggest that IL-17 is an in vitro stimulator of angiogenic factor release, both by its own action and by cooperating with TNF-alpha.
Osteoarthritis and Cartilage 05/2006; 14(4):345-52. · 3.90 Impact Factor
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ABSTRACT: Autologous chondrocyte implantation (ACI) has been successfully used for the treatment of osteochondral lesions of the talus. One of the main problems of this surgical strategy is related to the harvesting of the cartilage slice from a healthy knee. The aim of this study was to examine the capacity of chondrocytes harvested from a detached osteochondral fragment to proliferate and to serve as a source of viable cells for ACI in the repair of ankle cartilage defects.
Detached osteochondral fragments harvested from the ankle joint of 20 patients with osteochondral lesions of the talus served as the source of human articular cartilage specimens. All of the osteochondral lesions were chronic and of traumatic origin. In all cases, the fragments were utilized to evaluate the viability and proliferation of the cells, the histological appearance of the cartilage tissue and the expression of specific cartilage markers by real-time polymerase chain reaction (PCR). In the 16 patients scheduled for ACI, the expanded chondrocytes were used for chondrocyte implantation. In the other 4 patients, with lesion size <1.5cm(2), microfractures were created during the initial arthroscopic step. As a control group, 7 patients with comparable osteochondral lesions underwent the same surgery, but received chondrocytes harvested from the ipsilateral knee.
According to the American Orthopaedic Foot and Ankle Scoring (AOFAS) system, patients in the experimental group had a preoperative score of 54.2+/-16 points and a postoperative one of 89+/-9.6 points after a minimum follow-up time of 12 months (P<0.0005). The control group of patients had a preoperative score of 54.6+/-11.7 points and a postoperative one of 90.2+/-9.7 points at a minimum follow-up time of 12 months (P<0.0005). The clinical results of the two groups did not differ significantly from each other. Chondrocytes isolated from the detached fragments were highly viable, phenotypically stable, proliferated in culture and redifferentiated when grown within the three-dimensional scaffold used for ACI. The morphological and molecular characteristics of the cartilage samples obtained from the detached osteochondral fragments were similar to those of healthy hyaline articular cartilage.
The good results achieved with this strategy indicate that cells derived from the lesioned area may be useful in the treatment of osteochondral defects of the talus.
Osteoarthritis and Cartilage 07/2005; 13(7):601-7. · 3.90 Impact Factor
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ABSTRACT: Ligaments are complex structures that maintain the mechanical stability of the joint. Healing of injured ligaments involves the interactions of different cell types, local cellular environment, and the use of devices. To gain new information on the complex interactions between mesenchymal stem cells (MSCs) and a specific hyaluronan-based prototype scaffold (HYAFF, useful for ligament tissue engineering, short time-course experiments were performed to analyze the proliferation, vitality, and phenotype of MSCs grown on the scaffold. MSC proliferation was analyzed using the MTT test, during the early time points (2, 4, 6, days). Viability was assessed using calcein/acetyloxymethylester immunofluorescence dye and confocal microscopy analysis. Hyaluronic acid receptor (CD44), typical matrix ligament proteins (collagen type I, type III, laminin, fibronectin, actin), and chondrogenic/osteogenic markers (collagen type II and bone sialoprotein) were evaluated by immunohistochemistry. Our data demonstrated that MSC growth and viability were cell density-dependent. MSCs completely wrapped the fibers of the scaffold, expressed CD44, collagen type I, type III, laminin, fibronectin, and actin, and were negative to collagen type II and bone sialoprotein. These data demonstrate that MSCs survive well in the hyaluronan-based prototype ligament scaffold, as assessed after 2 days from seeding, and express CD44, a receptor important for scaffold interaction, and proteins responsible for the functional characteristics of the ligaments.
Journal of Biomedical Materials Research Part A 07/2005; 73(3):275-83. · 2.63 Impact Factor
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ABSTRACT: The Dideco "Pluricell System" is a commercially available closed device composed of an expansion chamber and a kit of certified reagents that allow haematopoietic stem cell expansion. We have expanded seven umbilical cord blood (UCB) samples following the manufacturer's instructions; two groups of irradiated NOD-SCID mice have been transplanted with expanded and nonexpanded cells from the same UCB, and bone marrow was analysed for the presence of human cells. Average UCB volume was 61.6+/-8.8 ml; mean nucleated cell content was 1090.5+/-189.9 x 10(6). Percentage and number of CD34+ cells were 0.37+/-0.13% and 3.9+/-1.2 x 10(6). After separation, CD34+ cell purity was 82+/-11%. Mean number of inoculated cells was 760 000; mean NC and CD34+ fold expansion at 12 days was 230.4+/-91.5 and 21.0+/-11.9. Both groups of mice showed successful engraftment: the percentage of human cells was higher in the group receiving expanded cells (3.4+/-2.01%) compared to the group receiving nonexpanded cells (1.5+/-0.66%) (P<0.00018, Mann-Whitney test). The cell population obtained after 12 days expansion consisted mainly of myeloid and megakaryocytic progenitors. The CD34+ antigen reached the maximum expression level at day 12 (7.5+/-2.0%). Analysis of lineage-markers for human myelomonocytic, megakaryocytic, B, T, CD34 and erythroid cells, gave evidence that all the lineages were represented in the marrow of transplanted mice.
Bone Marrow Transplantation 06/2005; 35(11):1101-6. · 3.75 Impact Factor
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ABSTRACT: In a previous research, we have shown that adequate levels of polyamines are required in transformed mouse fibroblasts for the correlated activations of MAPK subtypes (ERK and JNK) and caspases induced by etoposide and leading to apoptosis. We report now that the treatment of fibroblasts with etoposide also elicited a progressive and sustained increase of NF-kappaB activation. The DNA binding activity of p65 NF-kappaB subunit was increased up to approximately 4-fold and was accompanied by enhancement of p65 phosphorylation. A two days pre-treatment of fibroblasts with alpha-difluoromethylornithine (DFMO), which caused polyamine depletion, provoked a slight activating effect when given alone, but markedly inhibited the etoposide-induced increases in p65 DNA binding and phosphorylation. The NF-kappaB inhibiting effect of DFMO was prevented by the addition of exogenous putrescine, which restored the intracellular content of polyamines. Selective inhibitors of the etoposide-stimulated MAPK subtypes also reduced NF-kappaB activation. Moreover, pharmacological NF-kappaB inhibition reduced the increase in caspase activity and cell death elicited by etoposide, suggesting that NF-kappaB is involved in signaling to apoptosis. The results of the present study, together with our previous findings, suggest that polyamines play a permissive role in the pathways triggered by etoposide and leading to cell death of fibroblasts, by supporting the activation of MAPKs, NF-kappaB and caspases.
Amino Acids 11/2004; 27(2):207-14. · 3.25 Impact Factor
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ABSTRACT: We investigated the effect of the proinflammatory cytokine interleukin 17 (IL-17) on the lysis of osteosarcoma cells by human NK cells. NK cells and U-2 OS, MG-63, HOS osteosarcoma cell lines express the IL-17 receptor, the highest amount being found on U-2 OS. Pre-incubation of NK cells with IL-17 did not affect the cytotoxicity against osteosarcomas, that was increased when U-2 OS were pre-incubated with IL-17. In IL-17 treated U-2 OS osteosarcoma cells FACS analysis demonstrated an increased expression of fibronectin among the panel of adhesion molecules assayed, and the treatment with anti-fibronectin antibodies decreased the NK cytotoxicity. The comparison between interferon gamma (IFN-gamma) treated and IFN-gamma/IL-17-treated U-2 OS showed a decreased susceptibility to NK lysis associated with a reduced expression of CD49f on U-2 OS treated with IFN-gamma/IL-17. IL-17 appears to be a modulator of NK adhesion molecules on U-2 OS cells but antagonizes with IFN-gamma on NK lysis.
Clinical & Experimental Immunology 10/2003; 133(3):344-9. · 3.36 Impact Factor
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ABSTRACT: To evaluate in vivo expression of chemokine receptors in cartilage tissue samples from healthy and diseased joints.
Presence and distribution of several chemokine receptors in cartilage samples from patients with osteoarthritis (OA) or inflammatory arthritis (IA) and from multi-organ donors were assessed by immunohistochemistry. The expression of messenger RNA (mRNA) for chemokine receptors was also analysed by reverse transcriptase-polymerase chain reaction (RT-PCR).
Normal and OA-affected cartilage showed a moderate to high expression of chemokine receptors, while staining of IA samples ranged from low to absent. Differences between OA and IA samples were present for all receptors but CCR2 and CXCR4. Moreover, mRNAs for CCR1, CCR5 and CXCR1 were found both in normal and pathological chondrocytes, suggesting that chemokine receptor down-modulation seen in IA samples could be a post-transcriptional event.
Data on normal and pathological chondrocytes underline the role of chemokines in cartilage homeostasis and suggest an imbalance towards catabolic processes in inflammatory conditions.
Rheumatology 02/2003; 42(1):14-8. · 4.06 Impact Factor
