Artificial matrices with high-sulfated glycosaminoglycans and collagen are anti-inflammatory and pro-osteogenic for human mesenchymal stromal cells.
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.
Institute of Physiological Chemistry, Carl Gustav Carus Faculty of Medicine, TU Dresden, Fiedlerstrasse 42, D-01307, Dresden, Germany.
Ute
U
Hempel
Claudia
C
Matthäus
Carolin
C
Preissler
Stephanie
S
Möller
Vera
V
Hintze
Peter
P
Dieter
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D024042:Collagen Type I / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000737:chemistry / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010012:Osteogenesis / Q000187:drug effects; D013431:Sulfates / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D024042:Collagen Type I; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D013431:Sulfates
EXTRACELLULAR MATRIX; GLYCOSAMINOGLYCANS; INFLAMMATION; MESENCHYMAL STROMAL CELLS; OSTEOGENIC DIFFERENTIATION; PROSTAGLANDINS