title: Sulfated hyaluronan containing collagen matrices enhance cell-matrix-interaction, endocytosis, and osteogenic differentiation of human mesenchymal stromal cells.
abstract: Inorganic-organic composite implant materials mimicking the environment of bone are promising applications to meet the increasing demands on biomaterials for bone regeneration caused by extended life spans and the concomitant increase of bone treatments. Besides collagen type I (Col-I) glycosaminoglycans (GAG), such as hyaluronan, are important components of the bone extracellular matrix (ECM). Sulfated GAGs are potential stimulators of bone anabolic activity, as they are involved in the recruitment of mesenchymal stromal cells (MSCs) to the site of bone formation and support differentiation to osteoblasts. Nevertheless, no consecutive data is currently available about the interaction of hyaluronan or sulfated hyaluronan derivatives with hMSCs and the molecular processes being consequently regulated. We applied quantitative proteomics to investigate the influence of artificial ECM composed of Col-I and hyaluronan (Hya) or sulfated hyaluronan (HyaS3) on the molecular adaptation of osteogenic-differentiated human MSCs (hMSCs). Of the 1,370 quantified proteins, the expression of 4-11% was altered due to both aECM-combinations. Our results indicate that HyaS3 enhanced multiple cell functions, including cell-matrix-interaction, cell-signaling, endocytosis, and differentiation. In conclusion, this study provides fundamental insights into regulative cellular responses associated with HyaS3 and Hya as components of aECM and underlines the potential of HyaS3 as a promising implant-coating-material.
authors.affiliation: Department of Proteomics, Helmholtz-Centre for Environmental Research-UFZ, Permoserstrasse 15, 04318 Leipzig, Germany. Stefan.Kalkhof@ufz.de
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kliemt
authors.forename: Claudia
authors.initials: C
authors.lastname: Lange
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.forename: Vera
authors.initials: V
authors.lastname: Hintze
authors.forename: Stephanie
authors.initials: S
authors.lastname: Möller
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.forename: Ute
authors.initials: U
authors.lastname: Hempel
authors.forename: Stefan
authors.initials: S
authors.lastname: Kalkhof
mesh_terms: D000328:Adult; D001672:Biocompatible Materials / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D040901:Proteomics; D015398:Signal Transduction / Q000187:drug effects; D013431:Sulfates / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D006025:Glycosaminoglycans; D013431:Sulfates; D006820:Hyaluronic Acid