Hempel Ute, Matthäus Claudia, Preissler Carolin, Möller Stephanie, Hintze Vera, Dieter Peter
Institute of Physiological Chemistry, Carl Gustav Carus Faculty of Medicine, TU Dresden, Fiedlerstrasse 42, D-01307, Dresden, Germany.
J Cell Biochem. 2014 Sep;115(9):1561-71. doi: 10.1002/jcb.24814.
Bone healing has been described to be most efficient if the early inflammatory phase is resolved timely. When the inflammation elevates or is permanently established, bone healing becomes impaired and, moreover, bone destruction often takes place. Systemic disorders such as diabetes and bone diseases like arthritis and osteoporosis are associated with sustained inflammation and delayed bone healing. One goal of biomaterial research is the development of materials/surface modifications which support the healing process by inhibiting the inflammatory bone erosion and suppressing pro-inflammatory mediators and by that promoting the bone repair process. In the present study, the influence of artificial extracellular matrices (aECM) on the interleukin (IL)-1β-induced pro-inflammatory response of human mesenchymal stromal cells (hMSC) was studied. hMSC cultured on aECM composed of collagen I and high-sulfated glycosaminoglycan (GAG) derivatives did not secrete IL-6, IL-8, monocyte chemoattractant protein-1, and prostaglandin E2 in response to IL-1β. The activation and nuclear translocation of nuclear factor κBp65 induced by IL-1β, tumor necrosis factor-α or lipopolysaccharide was abrogated. Furthermore, these aECM promoted the osteogenic differentiation of hMSC as determined by an increased activity of tissue non-specific alkaline phosphatase (TNAP); however, the aECM had no effect on the IL-1β-induced TNAP activity. These data suggest that aECM with high-sulfated GAG derivatives suppress the formation of pro-inflammatory mediators and simultaneously promote the osteogenic differentiation of hMSC. Therefore, these aECM might offer an interesting approach as material/surface modification supporting the bone healing process.
如果早期炎症阶段能及时消退,骨愈合被认为是最有效的。当炎症加剧或持续存在时,骨愈合会受到损害,而且常常会发生骨质破坏。糖尿病等全身性疾病以及关节炎和骨质疏松症等骨疾病与持续炎症和骨愈合延迟有关。生物材料研究的一个目标是开发通过抑制炎症性骨侵蚀和抑制促炎介质来支持愈合过程,从而促进骨修复过程的材料/表面改性。在本研究中,研究了人工细胞外基质(aECM)对白细胞介素(IL)-1β诱导的人间充质基质细胞(hMSC)促炎反应的影响。在由I型胶原蛋白和高硫酸化糖胺聚糖(GAG)衍生物组成的aECM上培养的hMSC不会因IL-1β而分泌IL-6、IL-8、单核细胞趋化蛋白-1和前列腺素E2。由IL-1β、肿瘤坏死因子-α或脂多糖诱导的核因子κBp65的激活和核转位被消除。此外,这些aECM促进了hMSC的成骨分化,这通过组织非特异性碱性磷酸酶(TNAP)活性的增加来确定;然而,aECM对IL-1β诱导的TNAP活性没有影响。这些数据表明,具有高硫酸化GAG衍生物的aECM可抑制促炎介质的形成,同时促进hMSC的成骨分化。因此,这些aECM可能作为支持骨愈合过程的材料/表面改性提供一种有趣的方法。