title: Sulfated glycosaminoglycans support osteoblast functions and concurrently suppress osteoclasts.
abstract: In order to improve bone regeneration, development and evaluation of new adaptive biomaterials is warranted. Glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) are major extracellular matrix (ECM) components of bone, and display osteogenic properties that are potentially useful for biomaterial applications. Using native and synthetic sulfate-modified GAGs, we manufactured artificial collagen/GAG ECM (aECMs) coatings, and evaluated how the presence of GAGs and their degree of sulfation affects the differentiation of murine mesenchymal stem cells to osteoblasts (OB) cultivated on these aECMs. GAG sulfation regulated osteogenesis at all key steps of OB development. Adhesion, but not migration, was diminished by 50% (P < 0.001). Proliferation and metabolic activity were slightly (P < 0.05) and cell death events strongly (P < 0.001) down-regulated due to a switch from proliferative to matrix synthesis state. When exposed to sulfated GAGs, OB marker genes, such as alkaline phosphatase, osteoprotegerin (OPG), and osteocalcin increased by up to 28-fold (P < 0.05) and calcium deposition up to 4-fold (P < 0.05). Furthermore, GAG treatment of OBs suppressed their ability to support osteoclast (OC) differentiation and resorption. In conclusion, GAG sulfation controls bone cell homeostasis by concurrently promoting osteogenesis and suppressing their paracrine support of OC functions, thus displaying a favorable profile on bone remodeling. Whether these cellular properties translate into improved bone regeneration needs to be validated in vivo.
authors.affiliation: Dresden Technical University Medical Center, Dresden, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Salbach-Hirsch
authors.forename: Nicole
authors.initials: N
authors.lastname: Ziegler
authors.forename: Sylvia
authors.initials: S
authors.lastname: Thiele
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moeller
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnabelrauch
authors.forename: Vera
authors.initials: V
authors.lastname: Hintze
authors.forename: Dieter
authors.initials: D
authors.lastname: Scharnweber
authors.forename: Martina
authors.initials: M
authors.lastname: Rauner
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006025:Glycosaminoglycans / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D006025:Glycosaminoglycans; D053244:Osteoprotegerin; D015675:Osteocalcin; C013786:A73025; D003094:Collagen; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: CHONDROITIN SULFATE (CS); GLYCOSAMINOGLYCANS (GAG); HYALURONIC ACID/HYALURONAN (HA) SULFATE; OSTEOBLASTS (OB); OSTEOCLASTS (OC)