1,720,970 research outputs found
Basement membrane components are key players in specialized extracellular matrices
Full text linkMore than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches
Nidogen-1 and nidogen-2 in healthy human cartilage and in late-stage osteoarthritis cartilage
No full textObjective. To investigate the presence and function of nidogen-1 and nidogen-2 in healthy human cartilage and in late-stage osteoarthritis (OA) cartilage. Methods. The location and quantity of nidogen-1 and nidogen-2 protein and messenger RNA were determined in cartilage tissue obtained from healthy donors and from patients with late-stage knee OA. Samples were analyzed by immunohistochemistry, in situ hybridization, and real-time reverse transcription-polymerase chain reaction. Adhesion and inhibition assays, a preembedding method, fluorescence-activated cell sorting, and ultrastructural investigations with integrins were also carried out. Results. Developing tissue from human embryos showed strong staining for both nidogens in condensed mesenchyme and in rib anlagen. Homogeneous staining for nidogen-1 was observed in the extracellular matrix of healthy articular cartilage, whereas nidogen-2 was localized pericellularly. In late-stage OA cartilage, expression of nidogen-1 was decreased pericellularly around diseased chondrocytes, whereas nidogen-2 was increased. However, both nidogens had strongly increased levels around elongated chondrocytes, especially in areas of deep surface fissures. In vitro, both nidogens functioned as adhesion proteins for cells from the OA defect. In vivo, colocalizations with integrins alpha v and beta 1 as well as internalization of nidogens by chondrocytes in vitro were observed. Conclusion. Nidogens are involved in human limb development. They occur in healthy articular cartilage and show increased expression, primarily around elongated chondrocytes, in OA cartilage. Therefore, the activities of nidogens might be a sign of cartilage regeneration in late-stage OA. Furthermore, the adhesive character of nidogens, specifically as adhesion proteins for chondrocytes from late-stage OA, as well as the enhanced chondrocyte-nidogen interaction in OA indicate that both proteins play a key role in the pathogenesis of OA and either could be applied as a diagnostic marker
New insights into cartilage repair - The role of migratory progenitor cells in osteoarthritis
No full textOsteoarthritis is one of the most common musculo-skeletal diseases with a complex patholoy and a strong impact on cell biology, differentiation and migration behavior of mesenchymal stem cell-derived progenitor cells. In this review, we elucidate the influence of the pathologically altered extracellular matrix on progenitor cell behavior. Moreover, we discuss the modulation of progenitor cells especially of previously characterized chondrogenic progenitor cells (Koelling et al., 2009) in situ to enhance their regeneration potential. These options comprise the application of growth factors like fibroblast growth factor-2, a Runx-2 knock down and a contemporary anti-inflammatory therapy. This supports endogenous regeneration on behalf of the diseased osteoarthritic cartilage, which otherwise results mainly in an insufficient fibro-cartilaginous repair tissue. Furthermore, new results indicate a role of pericytes in osteoarthritis for these repair attempts. We discuss the biological mechanisms potentially leading to new therapeutic options in osteoarthritis to enhance regeneration in situ
BOTULINUM TOXIN: A NONINVASIVE OPTION FOR THE SYMPTOMATIC TREATMENT OF SALIVARY GLAND STENOSIS-A CASE REPORT
No full textBackground. A man diagnosed with Stensen's duct stenosis exhibited recurrent parotid swelling, invariably during meals. Previous parotid duct dilations and percutaneous radiotherapy were ineffective. Botulinum toxin (BTX) injections were injected into the affected gland to regulate salivary flow and reduce parotid swelling. Methods. BTX (22.5 units) was injected into the affected gland. A second treatment with 30 units BTX was carried out 7 weeks later. Two further injections followed after 4 months, respectively. The results were scored by the patient and evaluated in an examination. Results. The patient reported the disappearance of parotid swelling after 2 weeks of injections. This effect was maintained for 5 weeks after the first treatment and for 4 months after the following 2 treatments. There were no side effects. Conclusion. Here we introduce BTX as a therapeutic option for the treatment of salivary duct stenosis when other therapies are ineffective and before opting for gland extirpation. (c) 2009 Wiley Periodicals, Inc. Head Neck 32: 959-963, 201
Use of botulinum toxin in ORL departments in Germany
No full textThere are no regional data about the prevalence and use of botulinum toxin (BoNT) in otorhinolaryngology (ORL) departments in Germany. In order to obtain an overview of the current applications of BoNT in ORL departments a survey was carried out. Standardized multi-choice questionnaires were mailed to 150 ORL departments. In the analysis a differentiation was made between university and regional departments. Also an analysis of the whole collective of respondent hospitals was carried out. The most commonly treated indication is the Frey syndrome followed by hypersalivation due to a salivary fistula after parotidectomy, dysphagia, aesthetic application and laryngeal dystonia. The rate of return was 62% and 75% of all responding hospitals use BoNT as a therapeutic option, especially where "off-label-use" indications are concerned (15 out of 20 indications or 75%). BoNT is widely used as a therapeutic option with an increasing trend. Due to different applications a schedule of hospitals would be helpful in order to be able to find the nearest hospital for the appropriate indications
Tissue distribution of perlecan domains III and V during embryonic and fetal human development
No full textA major component of basement membranes (BMs) is perlecan, a five-domain heparan sulphate proteoglycan. During murine embryogenesis, nearly all BMs of mesenchymal origin express perlecan, and it is believed to participate in the supramolecular assembly of BMs. However, the distribution of perlecan in human embryonic and fetal tissues is widely unknown, except for cartilage anlagen of developing extremities and the fetal spine. Clinical syndromes, caused by perlecan-associated mutations or gene-defects, suggest its multifunctional involvement during human development. Here we reveal the immunohistochemistry of perlecan domains III and V during human development from gestational weeks (gw) 6 to 12 in basement membrane zones (BMZs) of the developing brain, nervous system, blood vessels, skin, lung, heart, kidney, liver, intestine and skeletal system. Interestingly, a difference in the distribution of the two perlecan domains was found in the endoneurium of ganglia. Domain III is strongly present from gw 6 onwards, while domain V shows attenuated expression at this stage and has been detected abundantly only from gw 8 onwards, possibly indicating vascularization of the endoneurium during this early stage. We found perlecan to be present particularly at those stages of human development where epithelial-mesenchymal interactions occur
The absence of one or both nidogens does not alter basement membrane composition in adult murine kidney
No full textNidogen- 1 and nidogen- 2 are major components of all basement membranes and are considered to function as link molecules between laminin and collagen type IV networks. Surprisingly, the knockout of one or both nidogens does not cause defects in all tissues or in all basement membranes. In this study, we have elucidated the appearance of the major basement membrane components in adult murine kidney lacking nidogen- 1, nidogen- 2, or both nidogens. To this end, we localized laminin- 111, perlecan, and collagen type IV in knockout mice, heterozygous (+/-) or homozygous (-/-) for the nidogen- 1 gene, the nidogen- 2 gene, or both nidogen genes with the help of light microscopic immunostaining. We also performed immunogold histochemistry to determine the occurrence of these molecules in the murine kidney at the ultrastructural level. The renal basement membranes of single knockout mice contained a similar distribution of laminin- 111, perlecan, and collagen type IV compared to heterozygous mice. In nidogen double- knockout animals, the basement membrane underlying the tubular epithelium was sometimes altered, giving a diffuse and thickened pattern, or was totally absent. The normal or thickened basement membrane of double- knockout mice also showed a similar distribution of laminin- 111, perlecan, and collagen type IV. The results indicate that the lack of nidogen- 1, nidogen- 2, or both nidogens, plays no crucial role in the occurrence and localization of laminin- 111, collagen type IV, and perlecan in murine tubular renal basement membranes
Tissue distribution of perlecan domains III and V during embryonic and fetal human development
No full textA major component of basement membranes (BMs) is perlecan, a five-domain heparan sulphate proteoglycan. During murine embryogenesis, nearly all BMs of mesenchymal origin express perlecan, and it is believed to participate in the supramolecular assembly of BMs. However, the distribution of perlecan in human embryonic and fetal tissues is widely unknown, except for cartilage anlagen of developing extremities and the fetal spine. Clinical syndromes, caused by perlecan-associated mutations or gene-defects, suggest its multifunctional involvement during human development. Here we reveal the immunohistochemistry of perlecan domains III and V during human development from gestational weeks (gw) 6 to 12 in basement membrane zones (BMZs) of the developing brain, nervous system, blood vessels, skin, lung, heart, kidney, liver, intestine and skeletal system. Interestingly, a difference in the distribution of the two perlecan domains was found in the endoneurium of ganglia. Domain III is strongly present from gw 6 onwards, while domain V shows attenuated expression at this stage and has been detected abundantly only from gw 8 onwards, possibly indicating vascularization of the endoneurium during this early stage. We found perlecan to be present particularly at those stages of human development where epithelial-mesenchymal interactions occur
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