title: Osteoblast-released Matrix Vesicles, Regulation of Activity and Composition by Sulfated and Non-sulfated Glycosaminoglycans.
abstract: Our aging population has to deal with the increasing threat of age-related diseases that impair bone healing. One promising therapeutic approach involves the coating of implants with modified glycosaminoglycans (GAGs) that mimic the native bone environment and actively facilitate skeletogenesis. In previous studies, we reported that coatings containing GAGs, such as hyaluronic acid (HA) and its synthetically sulfated derivative (sHA1) as well as the naturally low-sulfated GAG chondroitin sulfate (CS1), reduce the activity of bone-resorbing osteoclasts, but they also induce functions of the bone-forming cells, the osteoblasts. However, it remained open whether GAGs influence the osteoblasts alone or whether they also directly affect the formation, composition, activity, and distribution of osteoblast-released matrix vesicles (MV), which are supposed to be the active machinery for bone formation. Here, we studied the molecular effects of sHA1, HA, and CS1 on MV activity and on the distribution of marker proteins. Furthermore, we used comparative proteomic methods to study the relative protein compositions of isolated MVs and MV-releasing osteoblasts. The MV proteome is much more strongly regulated by GAGs than the cellular proteome. GAGs, especially sHA1, were found to severely impact vesicle-extracellular matrix interaction and matrix vesicle activity, leading to stronger extracellular matrix formation and mineralization. This study shows that the regulation of MV activity is one important mode of action of GAGs and provides information on underlying molecular mechanisms.
authors.affiliation: From the ‡Department of Proteomics, Helmholtz Centre for Environmental Research UFZ, 04318 Leipzig, Germany;
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Schmidt
authors.affiliation: From the ‡Department of Proteomics, Helmholtz Centre for Environmental Research UFZ, 04318 Leipzig, Germany;
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kliemt
authors.affiliation: the ‖Institute of Physiological Chemistry, TU Dresden, 01307 Dresden, Germany;
authors.forename: Carolin
authors.initials: C
authors.lastname: Preissler
authors.affiliation: the **Biomaterials Department, INNOVENT e.V., 07745 Jena, Germany;
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moeller
authors.affiliation: From the ‡Department of Proteomics, Helmholtz Centre for Environmental Research UFZ, 04318 Leipzig, Germany; the ‡‡Department of Metabolomics, Helmholtz Centre for Environmental Research UFZ, 04318 Leipzig, Germany; §§Department of Chemistry and Bioscience, Aalborg University, 9220 Aalborg East, Denmark;
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.affiliation: the ‖Institute of Physiological Chemistry, TU Dresden, 01307 Dresden, Germany; Stefan.Kalkhof@ufz.de Ute.Hempel@tu-dresden.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Hempel
authors.affiliation: From the ‡Department of Proteomics, Helmholtz Centre for Environmental Research UFZ, 04318 Leipzig, Germany; the ¶¶Department of Bioanalytics, University of Applied Sciences and Arts of Coburg, 96450 Coburg, Germany Stefan.Kalkhof@ufz.de Ute.Hempel@tu-dresden.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kalkhof
mesh_terms: D000328:Adult; D000375:Aging / Q000473:pathology*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D001862:Bone Resorption / Q000235:genetics* / Q000473:pathology; D018929:Cell Culture Techniques; D002809:Chondroitin Sulfates / Q000008:administration & dosage; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000008:administration & dosage; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage; D008297:Male; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods*
chemical_list: D006025:Glycosaminoglycans; D011506:Proteins; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates