Salbach-Hirsch Juliane, Ziegler Nicole, Thiele Sylvia, Moeller Stephanie, Schnabelrauch Matthias, Hintze Vera, Scharnweber Dieter, Rauner Martina, Hofbauer Lorenz C
Dresden Technical University Medical Center, Dresden, Germany.
J Cell Biochem. 2014 Jun;115(6):1101-11. doi: 10.1002/jcb.24750.
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.
为了改善骨再生，开发和评估新型适应性生物材料是很有必要的。糖胺聚糖（GAGs），如透明质酸（HA）和硫酸软骨素（CS），是骨的主要细胞外基质（ECM）成分，并具有成骨特性，这对生物材料应用可能有用。我们使用天然和合成的硫酸化修饰GAGs制备了人工胶原蛋白/GAG细胞外基质（aECMs）涂层，并评估了GAGs的存在及其硫酸化程度如何影响在这些aECMs上培养的小鼠间充质干细胞向成骨细胞（OB）的分化。GAG硫酸化在OB发育的所有关键步骤中调节骨生成。黏附能力降低了50%（P < 0.001），但迁移能力未受影响。由于从增殖状态转变为基质合成状态，增殖和代谢活性略有下调（P < 0.05），而细胞死亡事件则强烈下调（P < 0.001）。当暴露于硫酸化GAGs时，OB标记基因，如碱性磷酸酶、骨保护素（OPG）和骨钙素增加了高达28倍（P < 0.05），钙沉积增加了4倍（P < 0.05）。此外，用GAG处理OBs会抑制它们支持破骨细胞（OC）分化和吸收的能力。总之，GAG硫酸化通过同时促进骨生成和抑制它们对OC功能的旁分泌支持来控制骨细胞稳态，从而在骨重塑方面显示出良好的特性。这些细胞特性是否能转化为改善的骨再生需要在体内进行验证。
