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Papers by Sibylle Hoedt-Schmidt

PubMed, May 1, 1989

Fluorescein isothiocyanate (FITC) labelled lectins were applied to study the topographical locali... more Fluorescein isothiocyanate (FITC) labelled lectins were applied to study the topographical localisation and distribution of cellular as well as extracellular glycoconjugates in histological sections of normal and degenerative cartilage tissue. Using a biochemically induced model of osteoarthrosis (OA) in the knee joints of rats, the binding pattern of several lectins (wheat germ agglutinin (WGA), concanavalin A (Con A), Ulex europeus agglutinin I (UEA I), soybean agglutinin (SBA), and peanut agglutinin (PNA] in degenerative cartilage was compared with results obtained from normal healthy tissue. In response to osteoarthritic metabolic lesions the binding pattern of WGA revealed an increased cellular staining throughout the whole depth of the tissue which represents the compensatory activity of chondrocytes. The increased anabolic cell activity is maintained by enzymatic degradation of pericellular glycosaminoglycans. Osteoarthritic cartilage exposed positive fluorescence with labelled Con A demonstrating alterations in the composition of matrix glycoconjugates. The incubation of normal healthy cartilage tissue with UEA I, SBA, and PNA resulted in a completely negative staining pattern. In contrast, we could show that the affinity of UEA I to the extracellular matrix was high in degenerative cartilage indicating degradation of matrix macromolecules. The obtained data revealed a significant difference of the lectin-binding pattern between osteoarthritic and normal cartilage tissue. Therefore it can be concluded that lectins are useful histochemical tools to characterize alterations in the integrity of joint tissue by their specific binding patterns.

Steinkopff eBooks, 1986

Im Krankheitsverlauf der Arthrosis deformans spielen phasenhaft auftretende entzundliche Reaktion... more Im Krankheitsverlauf der Arthrosis deformans spielen phasenhaft auftretende entzundliche Reaktionen des Gelenkkapselgewebes eine nicht unerhebliche Rolle fur die subjektiv klinische Manifestation der Erkrankung. Die Aktivierung der Arthrose zu einem Stadium der schmerzhaften Manifestation leitet einen Circulus vitiosus ein, der zu einer weiteren Verschlechterung des arthrotischen Geschehens fuhren kann. Nach Otte (1979) beschreibt der Begriff Aktivierung die Induktion von Entzundungsphanomenen im Synovialgewebe durch Strukturschaden der Gelenkflachen.

International journal of experimental pathology, 1993

The intra-articular injection of iodoacetate into the knee joint of rats produced changes in the ... more The intra-articular injection of iodoacetate into the knee joint of rats produced changes in the articular cartilage which resembled those of osteoarthritis. It caused virtually total loss of many of the oxidative enzymes, indicating inhibition of the main oxidative pathways. Treatment with an anti-rheumatic drug had little early effect but ultimately led to partial restoration of these pathways. The reduced progression of cartilage degradation induced by this drug was accompanied by some unusual histological features.

Arzneimittel-Forschung, 1989

The integrity of cartilage matrix depends on the homeostasis of synthetic and degradative process... more The integrity of cartilage matrix depends on the homeostasis of synthetic and degradative processes. Any disturbance of the rate of synthesis and catabolism may alter the amount of matrix components (e.g. proteoglycans). Based upon a biochemically induced osteoarthrosis (OA) in the knee joints of rats we investigated the histomorphological alterations under therapy with diclofenac sodium by histological-histochemical grading. Lectin-binding techniques using labelled wheat germ agglutinin (WGA), concanavalin A (Con A), Ulex europeus agglutinin I (UEA I), soybean agglutinin (SBA), and peanut agglutinin (PNA) were applied to analyze the cellular as well as the extracellular glycoconjugates in situ. Lectin-binding patterns quantitatively describe the topographical localization of structural components of the cartilage matrix which carry certain sugar residues. The therapy of the experimental OA with diclofenac sodium (2.0 mg/kg s.c.) led to a marked reduction of cartilage degenerations....

Clinical and experimental rheumatology

International journal of experimental pathology, 1992

The chemically induced injury to articular cartilage, caused by two successive intra-articular in... more The chemically induced injury to articular cartilage, caused by two successive intra-articular injections of sodium iodoacetate, has been used in studies on the effects of anti-inflammatory and of potentially chondroprotective agents. It has been assumed that the injurious effects are caused by inhibition of the glycolytic pathway. In the present study this inhibition has been shown to be greater than expected from in vitro studies, and to influence equally other oxidative pathways. However, the response is clearly not a simple one in that some of the surface chondrocytes, and synovial lining cells in close proximity to the cartilage, show virtually no inhibition.

Lectin Methods and Protocols

Cartilage is a highly specialized connective tissue that consists of cells embedded within an abu... more Cartilage is a highly specialized connective tissue that consists of cells embedded within an abundant extracellular matrix. The extracellular matrix of articular cartilage is composed of several types of collagens, proteoglycans, glycoproteins, noncollagenous proteins, polysaccharides, and water (for review, see refs. 1 and 2). Besides type II collagen as a major constituent, the predominant proteoglycan of cartilage tissue is the large aggregating proteoglycan (aggrecan) consisting of a core protein to which glycosaminoglycans and N- as well as O-linked oligosaccharides are attached. This proteoglycan is able to form specific aggregates with hyaluronic acid and link protein.

Der Rheumatismus, 1986

Pharmacology, 1993

Enzymatic scavenging of .O-2 radicals by injections of superoxide dismutase has been described to... more Enzymatic scavenging of .O-2 radicals by injections of superoxide dismutase has been described to inhibit the free radical reactions resulting in tissue damage. Using a biochemically induced model of osteoarthritis (OA) in the knee joints of hens, we investigated the histomorphological alterations under therapy with recombinant human superoxide dismutase (rH-SOD) in various doses by histological-histochemical grading. Treatment of experimental OA with rH-SOD (0.1 mg/0.1 ml intra-articularly) led to a significant reduction in the intensity of cartilage degradation. The pathomorphological alterations in the osteoarthritic cartilage of hens treated with rH-SOD were quantitatively but not qualitatively different from the placebo-treated group. Our results indicate that rH-SOD exerts an inhibitory effect on the deleterious processes on articular cartilage tissue during the course of OA and may counteract cartilage degradations induced or accelerated by oxygen radicals.

Bone, 1995

We have previously reported the expression and production of parathyroid hormone-related protein ... more We have previously reported the expression and production of parathyroid hormone-related protein (PTHrP) by human osteoblasts in culture (J. Bone Min. Res. 10:17-25). In addition we have shown that production of the protein is regulated by treatment with glucocorticoids and 1,25 dihydroxyvitamin D 3. In this study we have investigated the effects of the growth factors, transforming growth factor beta (TGF/30 and epidermal growth factor (EGF) on production of PTHrP by osteoblasts in culture. Fragments of human bone obtained at surgery were explanted into culture. At confluence cells were passaged into multiwell dishes and treated for 72 hrs with growth factor. Conditioned medium was harvested and the PTHrP produced measured by immunoradiometric assay ('IRMA, Nichols Institute). The total protein content of the cell layer was determined by a modification of the Lowry assay. PTHrP production (fmol/mg cell layer protein) was 24+4, 22+6, 29+4, 54+8 for cells treated with 0, 0.02, 0.2 and 2 ng/ml human EGF respectively (n=6, values shown mean+SD, production by cells treated with 2ng/ml significantly different from control p<0,001). PTHrP production (fmol/mg cell layer protein) was 18_+3, 23+5, 23_.+4, 48+6 for cells treated with 0, 0.002, 0.02 and 0.2 ng/ml human TGFfl~ respectively (n=6, values shown mean+SD, production by cells treated with 0.2ng/ml significantly different from control p<0.001). These data suggest that PTHrP production by human osteoblasts can be modulated by growth factors in vitro. The regulation of PTHrP production by TGF and EGF may be important in the local regulation of bone turnover in vivo.

Aktuelle Rheumatologie, 1986

Histochemistry, 1993

Lectins have specificity for certain carbohydrate structures in macromolecules. Lectins are, ther... more Lectins have specificity for certain carbohydrate structures in macromolecules. Lectins are, therefore, useful histochemical tools for demonstrating the composition and localization of components of connective tissue matrices, such as articular cartilage. In order to assess the significance of observed lectin-binding patterns, experiments were performed in which monoclonal antibodies against chondroitin sulphate-and keratan sulphate-containing proteoglycans and link proteins were applied to sections of bovine articular cartilage after enzymatic digestion with chbndroitinase ABC and keratanase. The following conclusions were made: (1) Binding of peanut agglutinin (PNA) in the interterritorial matrix predominantly indicates the presence of keratan sulphate, but may also detect O-linked oligosaccharides of proteoglycans. (2) In normal cartilage wheat germ agglutinin (WGA) binds nearly exclusively to keratan sulphate. In cartilage degraded with chondroitinase ABC and keratanase this lectin may also detect carbohydrates in link protein due to enhanced accessibility. Binding of WGA to O-linked oligosaccharides may eventually occur. (3) In enzymatically digested cartilage matrix, staining with soybean agglutinin (SBA) may be due to link protein, but not to chondroitin sulphate, because specific breakdown of the glycosaminoglycan chain is required for binding of SBA. (4) Ulex europaeus agglutinin I (UEA I) binding sites are only detectable in digested cartilage matrix.