Szabolcs Felszeghy

Publications of Szabolcs Felszeghy

• Retinoids produced by macrophages engulfing apoptotic cells contribute to the appearance of transglutaminase 2 in apoptotic thymocytes.

  Authors: Eva Garabuczi, Beáta Kiss, Szabolcs Felszeghy, Gregory J Tsay, László Fésüs, Zsuzsa Szondy

  Amino acids. 10/2011;

  Transglutaminase 2 (TG2) has been known for a long time to be associated with the in vivo apoptosis program of various cell types including T cells. Though the expression of the enzyme was stronglyTransglutaminase 2 (TG2) has been known for a long time to be associated with the in vivo apoptosis program of various cell types including T cells. Though the expression of the enzyme was strongly induced in mouse thymocytes following apoptosis induction in vivo, no significant induction of TG2 could be detected, when thymocytes were induced to die by the same stimuli in vitro indicating that signals arriving from the tissue environment are required for the in vivo induction of the enzyme in apoptotic thymocytes. Previous studies have shown that one of these signals is transforming growth factor-β (TGF-β) which is released by macrophages engulfing apoptotic cells. Besides TGF-β, the TG2 promoter contains retinoic acid response elements as well. Here we show that in vitro retinoic acids, or TGF-β and retinoic acids together can significantly enhance the TG2 mRNA expression in dying thymocytes, and the apoptotic signal contributes to the TG2 induction. Inhibition of retinoic acid synthesis either by alcohol or retinaldehyde dehydrogenases significantly attenuates the in vivo induction of TG2 following apoptosis induction indicating that retinoids indeed might contribute in vivo to the apoptosis-related TG2 expression. What is more, the in vivo apoptosis induction in the thymus is accompanied by an enhanced retinoid-dependent transcriptional activity due to the enhanced retinoid synthesis by macrophages engulfing apoptotic cells. Our data reveal a new crosstalk between macrophages and apoptotic cells, in which apoptotic cell uptake-induced retinoid synthesis in macrophages enhances TG2 expression in the dying thymocytes.

• Cell adhesion molecules in stromal corneal dystrophies.

  Authors: Gabor Nemeth, Szabolcs Felszeghy, Annamaria Kenyeres, Nora Szentmary, Andras Berta, Ildiko Suveges, Laszlo Modis

  Histology and histopathology. 09/2008; 23(8):945-52.

  The aim of the present study was to investigate the expression pattern of different cell adhesion molecules in corneal stromal dystrophies. Fifteen corneal buttons from patients diagnosed with threeThe aim of the present study was to investigate the expression pattern of different cell adhesion molecules in corneal stromal dystrophies. Fifteen corneal buttons from patients diagnosed with three different types of stromal corneal dystrophies and healthy corneas were investigated. Paraffin embedded sections were stained immunohistochemically with monoclonal antibodies against human intercellular adhesion molecule-1 (ICAM-1), endothelial selectin (E-selectin) and endothelial cadherin (E-cadherin) using the avidin-biotin-peroxidase-complex technique. The sections were compared to normal eye bank controls. In corneas from granular dystrophy patients ICAM-1 was expressed focally in epithelial cells and in keratocytes, and expressed diffusely in endothelial cells. In corneas from macular dystrophy patients diffuse epithelial staining was observed and the stromal and endothelial expression was found to be similar to that of granular dystrophy. In lattice dystrophy, only the epithelial cells and endothelium were intensively positive for ICAM-1. E-selectin was not present on any layer of the corneal specimens. E-cadherin was observed only in the epithelium of all three types of corneal dystrophies. Normal corneas did not express any of the investigated adhesion molecules. We found different expression patterns of adhesion molecules in corneas from stromal dystrophies. Our results suggest that adhesion molecules may be involved in the pathogenesis of corneal stromal dystrophies.

• Hyaluronan accumulates around differentiating neurons in spinal cord of chicken embryos.

  Authors: Zoltán Mészár, Szabolcs Felszeghy, Gábor Veress, Klára Matesz, György Székely, László Módis

  Brain research bulletin. 04/2008; 75(2-4):414-8.

  One major component of the extracellular matrix is hyaluronan (HA) which is thought to play a crucial role in the development of different organs including the central nervous system (CNS). HA isOne major component of the extracellular matrix is hyaluronan (HA) which is thought to play a crucial role in the development of different organs including the central nervous system (CNS). HA is bound by specific receptors, CD44 and RHAMM, depending on cell types of CNS. However, data are lacking on the relation of HA to different cell populations in developing CNS. To provide new data about the co-localization of HA with the various cellular structures of the developing spinal cord, we studied the distribution pattern of hyaluronan in chicken embryos at Hamburger-Hamilton (HH) stages 8-39. A biotinylated HA-binding complex was used in combination with immunohistochemistry for proliferating and differentiating neurons. The intensity of the HA signal was determined by digital densitometry from histological sections. We found three mediolaterally oriented layers in the HA distribution pattern in stage HH23: (1) a moderate HA signal was detected in the ventricular zone; (2) strong HA accumulation was measured around Lim1,2-expressing cells (differentiating neurons) and early MNR2-expressing neurons (early motoneurons), corresponding to the intermediate zone; (3) a strong pericellular HA reaction was found around the neurons of the marginal zone. Interestingly, the peripheral nerves did not show HA signals. These findings suggest a crucial role of HA during neuronal development. We propose that HA may be involved in cell migration and axonal growth in the developing spinal cord.

• The effect of vestibular nerve section on the expression of the hyaluronan in the frog, Rana esculenta.

  Authors: Gábor Halasi, Ervin Wolf, Tímea Bácskai, György Székely, László Módis, Zsuzsa M Szigeti, Zoltán Mészár, Szabolcs Felszeghy, Clara Matesz

  Brain structure & function. 01/2008; 212(3-4):321-34.

  Following postganglionic lesion of the eighth cranial nerve, the changes in the expression of hyaluronan (HA), one of the extracellular matrix macromolecules, were examined in the medial (MVN) andFollowing postganglionic lesion of the eighth cranial nerve, the changes in the expression of hyaluronan (HA), one of the extracellular matrix macromolecules, were examined in the medial (MVN) and lateral (LVN) vestibular nuclei and in the entry or transitional zone (TZ) of the nerve in the frog. HA was detected in different survival times by using a specific biotinylated hyaluronan-binding probe. HA expression was defined by the area-integrated optical density (AIOD), calculated from pixel intensities of digitally captured images. During the first postoperative days the perineuronal net (PN), a HA-rich area around the neurons, was not distinguishable from the surrounding neuropil in the MVN and LVN, characterized by a bilateral drop of AIOD specifically on the operated side. From postoperative day 14 onwards AIOD increased whilst the PN reorganized. In contrast, the AIOD wobbled up and down bilaterally without any trend in the TZ. Statistical analysis indicated that AIOD changes in the structures studied ran parallel bilaterally presumably because of the operation. Our results demonstrated for the first time that (1) the lesion of the eighth cranial nerve is accompanied by the modification of AIOD reflected HA expression in the MVN, LVN and TZ, (2) different tendencies exist in the time course of AIOD in the structures studied and (3) these tendencies are similar on the intact and operated sides. Our findings may suggest an area dependent molecular mechanism of HA in the restoration of vestibular function.

• An integrated gene regulatory network controls stem cell proliferation in teeth.

  Authors: Xiu-Ping Wang, Marika Suomalainen, Szabolcs Felszeghy, Laura C Zelarayan, Maria T Alonso, Maksim V Plikus, Richard L Maas, Cheng-Ming Chuong, Thomas Schimmang, Irma Thesleff

  PLoS biology. 07/2007; 5(6):e159.

  Epithelial stem cells reside in specific niches that regulate their self-renewal and differentiation, and are responsible for the continuous regeneration of tissues such as hair, skin, and gut.Epithelial stem cells reside in specific niches that regulate their self-renewal and differentiation, and are responsible for the continuous regeneration of tissues such as hair, skin, and gut. Although the regenerative potential of mammalian teeth is limited, mouse incisors grow continuously throughout life and contain stem cells at their proximal ends in the cervical loops. In the labial cervical loop, the epithelial stem cells proliferate and migrate along the labial surface, differentiating into enamel-forming ameloblasts. In contrast, the lingual cervical loop contains fewer proliferating stem cells, and the lingual incisor surface lacks ameloblasts and enamel. Here we have used a combination of mouse mutant analyses, organ culture experiments, and expression studies to identify the key signaling molecules that regulate stem cell proliferation in the rodent incisor stem cell niche, and to elucidate their role in the generation of the intrinsic asymmetry of the incisors. We show that epithelial stem cell proliferation in the cervical loops is controlled by an integrated gene regulatory network consisting of Activin, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Follistatin within the incisor stem cell niche. Mesenchymal FGF3 stimulates epithelial stem cell proliferation, and BMP4 represses Fgf3 expression. In turn, Activin, which is strongly expressed in labial mesenchyme, inhibits the repressive effect of BMP4 and restricts Fgf3 expression to labial dental mesenchyme, resulting in increased stem cell proliferation and a large, labial stem cell niche. Follistatin limits the number of lingual stem cells, further contributing to the characteristic asymmetry of mouse incisors, and on the basis of our findings, we suggest a model in which Follistatin antagonizes the activity of Activin. These results show how the spatially restricted and balanced effects of specific components of a signaling network can regulate stem cell proliferation in the niche and account for asymmetric organogenesis. Subtle variations in this or related regulatory networks may explain the different regenerative capacities of various organs and animal species.

• Distribution of hyaluronan in the central nervous system of the frog.

  Authors: Zsuzsa M Szigeti, Clara Matesz, George Szekely, Szabolcs Felszeghy, Timea Bácskai, Gábor Halasi, Zoltán Mészár, László Módis

  The Journal of comparative neurology. 07/2006; 496(6):819-31.

  The qualitative and quantitative distribution pattern of hyaluronan (HA), a component of the extracellular matrix (ECM), was studied in the frog central nervous system by using a highly specific HAThe qualitative and quantitative distribution pattern of hyaluronan (HA), a component of the extracellular matrix (ECM), was studied in the frog central nervous system by using a highly specific HA probe and digital image analysis. HA reaction was observed in both the white and the gray matter, showing a very intense staining around the perikarya and dendrites in the perineuronal net (PN). In the telencephalon, strong reaction was found in different parts of the olfactory system, in the pallium, and in the amygdala. In the diencephalon, intensive staining was found in the nucleus of Bellonci, the dorsal habenula, the lateral and central thalamic nuclei, and the subependymal zone of the third ventricle. In the mesencephalon, layers of optic tectum displayed different intensities, with the strongest reaction in layers B, D, F, 3, and 5. Other structures of the mesencephalon showed regional differences. The PN was especially intensively stained around the perikarya of the toral nuclei, the oculomotor and trochlear nuclei, and the basal optic nucleus. In the rhombencephalon, the granular layer of cerebellum, the vestibulocochlear nuclei, the superior olive, the spinal tract of the trigeminal nerve, and parts of the reticular formation showed the most intense reaction in the PN. In the spinal cord, considerable HA staining was found in the white matter and around the perikarya of motoneurons. The present study is the first description of the HA-positive areas of frog brain and spinal cord demonstrating the heterogeneity of HA distribution in the frog central nervous system.

• Extracellular matrix molecules and their possible roles in the regeneration of frog nervous system.

  Authors: Clara Matesz, Laszlo Modis, Gabor Halasi, Zsuzsa M Szigeti, Szabolcs Felszeghy, Timea Bacskai, György Szekely

  Brain research bulletin. 10/2005; 66(4-6):526-31.

  Recent biochemical and histochemical analyses explored different components of the extracellular matrix (ECM) in the nervous system, and either permissive or non-permissive roles in neuronalRecent biochemical and histochemical analyses explored different components of the extracellular matrix (ECM) in the nervous system, and either permissive or non-permissive roles in neuronal development and regeneration were suggested. The aim of this study was to detect the distribution pattern of a few of these molecules in the nervous system of intact frogs and during nerve regeneration. The hyaluronan (HA) and tenascin C reactions were negative in the peripheral nerves, but appeared in their entry zones. In the CNS, different populations of neurons were surrounded with HA and tenascin C-positive material, forming a perineuronal net (PN). The phosphacan reaction was weakly positive in the PNS, and a moderate intensity was detected in the entry zone and in the PN. Laminin and fibronectin immunoreactivity was strong in the PNS, but laminin could not be detected in the CNS. In animals with cut and regenerating vestibulocochlear nerve, the distribution of the ECM molecules in the CNS and PNS characteristically changed from that of the normal pattern. Our results showed a non-homogenous distribution of ECM components in the frog nervous system that could be associated with their different roles in physiological and pathological processes.

• Measuring carotid artery stenosis--comparison of postmortem arteriograms with the planimetric gold standard.

  Authors: Gernot Schulte-Altedorneburg, Dirk W Droste, Józef Kollár, Torsten Beyna, Szabolcs Felszeghy, László Módis, Csaba Hegedüs, E Bernd Ringelstein, László Csiba

  Journal of neurology. 06/2005; 252(5):575-82.

  OBJECTIVE: Five different calliper methods for assessing the degree of carotid artery stenosis and visual estimation ("eyeballing") of postmortem carotid arteriograms were compared with theOBJECTIVE: Five different calliper methods for assessing the degree of carotid artery stenosis and visual estimation ("eyeballing") of postmortem carotid arteriograms were compared with the planimetric gold standard of the area reduction at the site of the stenosis. METHODS: During autopsy 53 carotid specimens were removed in toto from 31 neurological patients. Carotid arteries were ligated and redistended to a physiological degree for standardised three-plane arteriography. Afterwards, the entire specimen was filled with an embedding medium under the same conditions and sectioned. Slices at the site of stenoses were histologically processed. Computerised planimetric analysis of the lumen area reduction was performed and compared with the arteriographic findings. Arteriograms were evaluated by two independent observers by means of linear Common Carotid Artery (CC), the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and squared measurements (NASCET2, ECST2) after applying the pi r2 function. Further, three independent observers performed eyeballing of the degree of stenosis from the postmortem arteriographies. RESULTS: Planimetry was carried out in 29 internal carotid artery (ICA) and 17 common carotid artery (CCA) stenoses ranging from 8.5 to 100%. The smallest mean differences of the degree of stenosis in % between planimetry and arteriography were -0.5 and 0.6%. The narrowest 95 %-limits of agreement covered a range of +/-24.1 and 26.3% of stenoses, and the highest correlation coefficients were both 0.9 for the CC and ECST2 techniques, respectively. By eyeballing, the degree of stenosis was underestimated by 13.5 to 15.8% on average. The narrowest limits of agreement between two observers for eyeballing covered a range of 35%. CONCLUSION: Three-plane arteriography has only a moderate accuracy and reproducibility in detecting and measuring carotid artery stenosis independent of the technique of measurement used.

• Miller Fisher syndrome--a presenting clinical manifestation of lung cancer in a previously apparently healthy individual.

  Authors: Tünde Csépány, Judit Boczán, Mária T Magyar, Sándor Molnár, László Csiba, Judit Décsy, Judit Tóth, Szabolcs Felszeghy, Szabolcs Szakáll, Zsolt Szentkereszty, Dániel Bereczki

  Journal of neurology. 08/2004; 251(7):898-900.

• Detection of carotid artery stenosis by in vivo duplex ultrasound: correlation with planimetric measurements of the corresponding postmortem specimens.

  Authors: Gernot Schulte-Altedorneburg, Dirk W Droste, Szabolcs Felszeghy, László Csiba, Vasile Popa, Katalin Hegedüs, József Kollár, László Módis, E Bernd Ringelstein

  Stroke; a journal of cerebral circulation. 11/2002; 33(10):2402-7.

  BACKGROUND AND PURPOSE: The correct detection and quantification of carotid artery disease are of decisive impact on patient prognosis and adequate treatment. In this study, we evaluated the abilityBACKGROUND AND PURPOSE: The correct detection and quantification of carotid artery disease are of decisive impact on patient prognosis and adequate treatment. In this study, we evaluated the ability of ultrasonography to detect and to grade carotid artery stenosis through a comparison of the in vivo ultrasound findings with the planimetric analysis of the corresponding postmortem specimens. METHODS: Shortly before their death, 59 critically ill neurological patients (mean age, 70 years) were prospectively examined by extracranial and intracranial Doppler sonography and color-coded duplex ultrasound. Carotid stenosis was classified by hemodynamic and morphological ultrasound criteria. Carotid specimens were removed in toto during autopsy. Under standardized conditions, specimens were redistended, sectioned, and histologically processed. Computerized planimetric measurements of the arteries were carried out and compared with the ultrasound findings. Correlation of the ultrasound and postmortem planimetric findings was available in 93 carotid bifurcations. RESULTS: Through both techniques, 46 carotid arteries were found to be normal. Steno-occlusive carotid lesions ranged from 8.5% to 100% lumen reduction. Overall, r=0.96 and adjusted R(2)=0.90. For the steno-occlusive carotid lesions, r=0.91. CONCLUSIONS: Extracranial and intracranial Doppler and color-coded duplex ultrasound permits reliable detection and quantification of carotid artery stenoses and occlusions even under difficult examination conditions in critically ill patients.

• Protein phosphatase 2A is involved in the regulation of protein kinase A signaling pathway during in vitro chondrogenesis.

  Authors: Róza Zákány, Kornélia Szucs, Eva Bakó, Szabolcs Felszeghy, Gabriella Czifra, Tamás Bíró, László Módis, Pál Gergely

  Experimental cell research. 05/2002; 275(1):1-8.

  We have evaluated the importance of the Ser/Thr protein phosphorylation and dephosphorylation for chondrogenesis in high-density chicken limb bud mesenchymal cell cultures (HDCs) by using H89, aWe have evaluated the importance of the Ser/Thr protein phosphorylation and dephosphorylation for chondrogenesis in high-density chicken limb bud mesenchymal cell cultures (HDCs) by using H89, a cell-permeable protein kinase inhibitor, and okadaic acid (OA), a phosphoprotein phosphatase (PP)-specific inhibitor molecule. When 20 nM OA was applied to the HDCs on Days 2 and 3 of culturing, it significantly inhibited protein phosphatase 2A (PP2A), enhanced cartilage formation, and elevated the activity of cAMP-dependent protein kinase (PKA). Application of 20 microM H89 significantly decreased the activity of PKA and blocked the chondrogenesis in HDCs. Furthermore, OA enhanced cartilage formation and elevated the suppressed activity of PKA even in the H89-pretreated HDCs. cGMP-dependent protein kinase was not detected in HDCs, while protein kinase Cmu (PKCmu), which is also inhibited by nanomolar concentrations of H89, was present throughout the culturing period. Neither OA nor H89 influenced the expression of the catalytic subunit of PKA or the cAMP response element binding protein, CREB. However, a significantly elevated amount of Ser-133-phosphorylated-CREB (P-CREB) was detected following addition of OA, while H89 treatment resulted in a decrease of the amount of P-CREB. Our results demonstrate that PP2A plays a role in the regulation of the PKA signaling pathway and that the phosphorylation level of CREB is influenced by the activity of both enzymes during in vitro chondrogenesis.

• Notch signalling is required for the survival of epithelial stem cells in the continuously growing mouse incisor.

  Authors: Szabolcs Felszeghy, Marika Suomalainen, Irma Thesleff

  Differentiation; research in biological diversity. 80(4-5):241-8.

  The Notch pathway regulates the renewal and fate decisions of stem cells in multiple tissues. Notch1, -2, as well as the Notch target gene Hes1 are expressed in the putative stem cells in theThe Notch pathway regulates the renewal and fate decisions of stem cells in multiple tissues. Notch1, -2, as well as the Notch target gene Hes1 are expressed in the putative stem cells in the continuously growing mouse incisors, but so far there has not been any evidence for a function of the Notch pathway in the regulation of the incisor stem cells. We have analysed the effects of the Notch pathway inhibitor DAPT on the maintenance, proliferation, and differentiation of the epithelial stem cells in explant cultures of the mouse incisor. The proximal part of the incisor containing the cervical loop stem cell niche was dissected from newborn mice and cultured for 2-6 days in vitro. DAPT inhibited the expression of Notch target gene Hes1 in the cervical loop indicating that Notch signalling was inhibited in the putative stem cells. The most striking effect of DAPT was a significant reduction in the size of the cervical loop. DAPT caused a marked but partially reversible decrease in cell proliferation, as well as massive apoptosis in the epithelial stem cell niche. Interestingly, restricted apoptosis was detected within the Notch expressing putative stem cells also in the control cultures as well as in incisors in vivo, suggesting that apoptosis may be a mechanism regulating the size of the epithelial stem cell pool in the incisor. The differentiation of the epithelial cells into enamel-forming ameloblasts was not affected by DAPT but the number of preameloblasts was progressively decreased during culture period reflecting the depletion of stem and progenitor cells. Our results indicate that Notch signalling is required for epithelial stem cell survival and enamel formation in the continuously growing mouse incisor.

• Splitting placodes: effects of bone morphogenetic protein and Activin on the patterning and identity of mouse incisors.

  Authors: Pauliina M Munne, Szabolcs Felszeghy, Maria Jussila, Marika Suomalainen, Irma Thesleff, Jukka Jernvall

  Evolution & development. 12(4):383-92.

  The single large rodent incisor in each jaw quadrant is evolutionarily derived from a mammalian ancestor with many small incisors. The embryonic placode giving rise to the mouse incisor isThe single large rodent incisor in each jaw quadrant is evolutionarily derived from a mammalian ancestor with many small incisors. The embryonic placode giving rise to the mouse incisor is considerably larger than the molar placode, and the question remains whether this large incisor placode is a developmental requisite to make a thick incisor. Here we used in vitro culture system to experiment with the molecular mechanism regulating tooth placode development and how mice have thick incisors. We found that large placodes are prone to disintegration and formation of two to three small incisor placodes. The balance between one large or multiple small placodes was altered through the regulation of bone morphogenetic protein (BMP) and Activin signaling. Exogenous Noggin, which inhibits BMP signaling, or exogenous Activin cause the development of two to three incisors. These incisors were more slender than normal incisors. Additionally, two inhibitor molecules, Sostdc1 and Follistatin, which regulate the effects of BMPs and Activin and have opposite expression patterns, are likely to be involved in the incisor placode regulation in vivo. Furthermore, inhibition of BMPs by recombinant Noggin has been previously suggested to cause a change in the tooth identity from the incisor to the molar. This evidence has been used to support a homeobox code in determining tooth identity. Our work provides an alternative interpretation, where the inhibition of BMP signaling can lead to splitting of the large incisor placode and the formation of partly separate incisors, thereby acquiring molar-like morphology without a change in tooth identity.

• Az ép és kóros porcszövet változása in vitro kísérletekben = Alteration of normal and pathological cartilage tissue under in vitro conditions

  Authors: László Módis, Szabolcs Felszeghy, Levente Gáspár, Zoltán Mészár, Péter Molnár, Zoltán Szekanecz, Krisztina Szentesiné dr. Holló, Róza Zákány

  Pályázati ciklusunk 4 éve alatt az alábbi fontosabb eredményeket értük el: 1. A porcosodó "high-density" sejtkultúrákon végzett kísérleteinkkel kimutattuk, hogy az oxidatív stressz csökkenti aPályázati ciklusunk 4 éve alatt az alábbi fontosabb eredményeket értük el: 1. A porcosodó "high-density" sejtkultúrákon végzett kísérleteinkkel kimutattuk, hogy az oxidatív stressz csökkenti a képződő porc mennyiségét és az osztódó sejtek proliferációs képességét. Az oxidatív stressz a kalcineurin (PP2B) aktivitását és expresszióját csökkenti, míg az ERK és a Sox9 foszforilációja fokozódott. A kalcineurin farmakológiai inhibítora a ciklosporin hasonló hatással van a kultúrákra (Zákány és mtsai, 2005). 2. A mozaikplasztika továbbfejlesztése során humán műtéteket követően vett biopsziás minták hisztokémiai vizsgálatával igazoltuk, hogy a graft és host hialin porca és csontja az esetek döntő többségében tökéletesen fúzionál, a graft hialin porca csak néhány esetben alakul át rostos porccá (Hangody és mtsai, 2004; Hangody és Módis, 2006). Állatkísérletekkel igazoltuk, hogy a használt graft átmérőjének növelése stabilabb beépülést eredményez (Kordas és mtsai, 2006). Szövettani vizsgálataink során megerősítést nyert, hogy a mozaikplasztika lovakon is sikerrel végezhető (Bodó és mtsai, 2004). A donor-csatornák keletkezésével okozott komplikációk (vérzés) csökkentésére a PolyAktív biodegradábilis tömeszelőanyag jól alkalmazható (Bartha és mtsai, 2008). 3. Bizonyítottuk, hogy a makrofágok kulcsfontosságúak a RA patogenezisében. (Szekanecz és Koch, 2007). Rámutattunk az angiogenezist befolyásoló lehetőségekre az RA-terápiájában (Szekanecz és mtsai, 2005). | The following major new results were obtained: 1. Using chondrifying high density mesenchymal cell culture, we could detect that the oxidative stress decreases the chondrogenesis and the proliferation of chondrocytes. The oxidative stress decreases the activity and expression of calcineurin (PP2B), but the phosphorylation of ERK and Sox9 is elevated. Cyclosporine A, had the same effects on these cultures (Zákány et al, 2005). 2. In order to the further development of the mosaicplasty (MP), human biopsy samples taken after MP were analyzed histochemically. We demonstrated a complete fusion of the hyaline cartilage and bone of the donor and recipient areas in most cases. Exceptionally, the hyaline cartilage of the grafts is transformed to fibrocartilage (Hangody et al, 2004, Hangody and Módis, 2006). Using animal experiments, we came to the conclusion that the incorporation of the grafts can be improved by increasing the diameters of the grafts (Kordas et al, 2006). Clinical and histological investigations provided evidences about the successful application of MP also in horses (Bodo et al, 2004). To avoid the bleeding from the donor site, a biodegradable polymer material, polyactive, was successfully used for donor site filling in human MPs (Bartha et al, 2008). 3. We elucidated that macrophages can be regarded as possible target cells in the therapy of RA (Szekanecz and Koch, 2007). Therapy of RA by influencing angiogenesis is also discussed (Szekanecz et al, 2005).