RESUMO
BACKGROUND: In this study, the effect of 15-month anti-tumor necrosis factor alpha (TNF-α) treatment on circulating levels of plasma sulfated glycosaminoglycans (GAGs) and the nonsulfated GAG hyaluronic acid (HA) in female rheumatoid arthritis (RA) patients was assessed. METHODS: Plasma was obtained from healthy subjects and RA women treated with TNF-α antagonists (etanercept or adalimumab or certolizumab pegol) in combination with methotrexate. GAGs were isolated from plasma samples using ion exchange low-pressure liquid chromatography. Total sulfated GAGs were quantified using a hexuronic acid assay. Plasma levels of keratan sulfate (KS) and HA were measured using immunoassay kits. RESULTS: Total sulfated GAGs and HA levels were higher in female RA patients before treatment in comparison to healthy subjects. KS levels did not differ between RA women and controls. Anti-TNF-α treatment resulted in normalization of plasma total GAG and HA levels in RA patients, without any effect on KS levels. CONCLUSIONS: Our results suggest that anti-TNF-α therapy has a beneficial effect on extracellular matrix remodeling in the course of RA.
Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Glicosaminoglicanos/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/administração & dosagem , Adulto , Biomarcadores/sangue , Certolizumab Pegol/administração & dosagem , Quimioterapia Combinada , Etanercepte/administração & dosagem , Feminino , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Dermatan sulfate (DS) widespread as a component of extracellular matrix proteoglycans, is characterized by great bio-reactivity and remarkable structural heterogeneity due to distinct degrees of sulfation and glucuronosyl epimerization and different polymerization degrees. However, DS metabolism under various biological conditions is poorly known. Dupuytren's contracture is a benign fibromatosis leading to complex remodeling of the palmar fascia structure and properties. However, it remains unclear whether the disease affects the structure of DS, which is the major tissue glycosaminoglycan. Thus the aim of the study was to examine the structure of the total DS in Dupuytren's fascia. DS chains were extracted from 5 samples of normal fascia and 7 specimens of Dupuytren's tissue by papain digestion followed by fractionation with cetylpyridinium chloride. Then, DS structure analysis was performed comprising the evaluation of its molecular masses and sensitivity to hyaluronidase and chondroitinase B. Dupuytren's contracture is associated with significant remodeling of DS chain structure revealed by (1) a distinct profile of chain molecular masses characterized by the appearance of long size components as well as the increase in the content of small size chains; (2) a different glucuronosyl epimerization pattern connected with the enhanced content of glucuronate disaccharide blocks; (3) chain oversulfation. These structural alterations in total DS may modify the GAG interactions especially affecting collagen fibrillogenesis and growth factor availability. Thus, Dupuytren's contracture associated DS remodeling may promote the phenomena typical for advanced disease: apoptosis and reduction in cell number as well as the appearance of dense pseudotendinous collagen matrix.
Assuntos
Dermatan Sulfato/metabolismo , Contratura de Dupuytren/metabolismo , Configuração de Carboidratos , Dermatan Sulfato/química , Eletroforese em Gel de Poliacrilamida , HumanosRESUMO
Dupuytren's disease is a palmar fibromatosis associated with changes in fibroblast activity that also affect the metabolism of extracellular matrix components. In contrast to disease connected alterations in collagen and non-collagenous glycoproteins (mainly fibronectin), the metabolism of proteoglycans, being glycosaminoglycan modified glycoproteins, is poorly understood. Thus, the aim of the present study was the characterization of matrix proteoglycans (PGs) derived from normal fascia and Dupuytren's fascia. Extracted and purified PGs (particularly small PGs) were analysed for content, molecular mass, immunoreactivity and glycosaminoglycan chain structure. The matrix of normal fascia mainly contains decorin [small dermatan sulfate (DS) PG] with biglycan (another small DSPG) and large chondroitin sulfate(CS)/DSPG representing minor components. Dupuytren's disease is associated with the remodeling of matrix PG composition. The most prominent alteration is an accumulation of biglycan frequently bearing DS chains with higher molecular masses. Moreover, the amount of large CS/DSPG is increased. In contrast, decorin displays changes affecting mainly DS chain structure reflected in (i) an increase in some chain molecular masses, (ii) an enhanced content of iduronate disaccharide clusters, and (iii) oversulfation of disaccharide repeats. The PG alterations observed in Dupuytren's fascia may influence the matrix properties and contribute to disease progression.
Assuntos
Contratura de Dupuytren/patologia , Matriz Extracelular/fisiologia , Fáscia/química , Proteoglicanas/química , Adulto , Idoso , Biglicano , Cromatografia em Gel , Decorina , Contratura de Dupuytren/imunologia , Contratura de Dupuytren/fisiopatologia , Eletroforese em Gel de Poliacrilamida , Proteínas da Matriz Extracelular , Fáscia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteoglicanas/imunologiaRESUMO
The use of biological materials in construction of bioprostheses requires the application of different chemical or physical procedures of fixation increasing bioprostheses resistance to enzymatic or chemical degradation and reducing their antigenicity. Methods typically concentrate on creating additional intra- and intermolecular chemical bonds between collagen molecules. This review focuses on the various methods of stabilization of collagenous tissues including chemical fixatives and physical agents.