title: Artificial extracellular matrices with oversulfated glycosaminoglycan derivatives promote the differentiation of osteoblast-precursor cells and premature osteoblasts.
abstract: Sulfated glycosaminoglycans (GAG) are components of the bone marrow stem cell niche and to a minor extent of mature bone tissue with important functions in regulating stem cell lineage commitment and differentiation. We anticipated that artificial extracellular matrices (aECM) composed of collagen I and synthetically oversulfated GAG derivatives affect preferentially the differentiation of osteoblast-precursor cells and early osteoblasts. A set of gradually sulfated chondroitin sulfate and hyaluronan derivatives was used for the preparation of aECM. All these matrices were analysed with human bone marrow stromal cells to identify the most potent aECM and to determine the influence of the degree and position of sulfate groups and the kind of disaccharide units on the osteogenic differentiation. Oversulfated GAG derivatives with a sulfate group at the C-6 position of the N-acetylglycosamine revealed the most pronounced proosteogenic effect as determined by tissue nonspecific alkaline phosphatase activity and calcium deposition. A subset of the aECM was further analysed with different primary osteoblasts and cell lines reflecting different maturation stages to test whether the effect of sulfated GAG derivatives depends on the maturation status of the cells. It was shown that the proosteogenic effect of aECM was most prominent in early osteoblasts.
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fiedlerstraße 42, 01307 Dresden, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hempel
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fiedlerstraße 42, 01307 Dresden, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Preissler
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fiedlerstraße 42, 01307 Dresden, Germany.
authors.forename: Sarah
authors.identifier: 0000-0002-2944-4073
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Biomaterials Department, INNOVENT e. V., Prüssingstraße 27 B, 07745 Jena, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Möller
authors.affiliation: Max Bergmann Center of Biomaterials, TU Dresden, Budapester Straße 27, 01069 Dresden, Germany.
authors.forename: Vera
authors.identifier: 0000-0002-5611-9903
authors.initials: V
authors.lastname: Hintze
authors.affiliation: Biomaterials Department, INNOVENT e. V., Prüssingstraße 27 B, 07745 Jena, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Becher
authors.affiliation: Biomaterials Department, INNOVENT e. V., Prüssingstraße 27 B, 07745 Jena, Germany.
authors.forename: Matthias
authors.identifier: 0000-0002-1968-8058
authors.initials: M
authors.lastname: Schnabelrauch
authors.affiliation: Division of Endocrinology and Bone Diseases, Department of Medicine III, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Rauner
authors.affiliation: Division of Endocrinology and Bone Diseases, Department of Medicine III, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fiedlerstraße 42, 01307 Dresden, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dieter
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006025:Glycosaminoglycans / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; C013786:A73025; D000469:Alkaline Phosphatase; D002118:Calcium