title: The stimulation of an osteogenic response by classical monocyte activation.
abstract: The monocyte/macrophage system plays a central role in host defense, wound healing and immune regulation at biomaterial surfaces. Monocytes can be classically and alternatively activated, and can be stimulated differently in response to variations in biomaterial surface properties. In this study, human monocytes, cultured on polystyrene surfaces (Ps), were activated either classically, by lipopolysaccharide (LPS), or alternatively, by interleukin-4 (IL-4). Monocytes were also cultured on anodically oxidized (Ox) and machined (Ma) titanium surfaces, with and without LPS stimulation. Cells were cultured for 1 and 3 days and their conditioned media (CM) were collected. The osteogenic response of hMSCs to the monocyte CM was determined by analyzing the gene expression of key osteogenic markers. The CM from classically activated monocytes increased the hMSCs expression of runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). Furthermore, CM from monocytes cultured on Ox surface resulted in a modest increase of the expression of bone morphogenetic protein-2 (BMP-2). LPS stimulation of the surface-seeded monocytes overwhelmed the effect of the surface properties and resulted in significant upregulation of BMP-2 and Runx2 for all samples. The results show that human monocytes, cultured on different surfaces and/or under different activation pathways, communicate pro-osteogenic signals to hMSCs. The signals involve regulation of autologous BMP-2 in the hMSCs. The classical activation results in profound and prolonged osteogenic effect compared to the effect of the investigated surface properties.
authors.affiliation: Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, SE-405 30 Göteborg, Sweden. omar.omar@biomaterials.gu.se
authors.forename: Omar M
authors.initials: OM
authors.lastname: Omar
authors.forename: Cecilia
authors.initials: C
authors.lastname: Granéli
authors.forename: Karin
authors.initials: K
authors.lastname: Ekström
authors.forename: Camilla
authors.initials: C
authors.lastname: Karlsson
authors.forename: Anna
authors.initials: A
authors.lastname: Johansson
authors.forename: Jukka
authors.initials: J
authors.lastname: Lausmaa
authors.forename: Cecilia Larsson
authors.initials: CL
authors.lastname: Wexell
authors.forename: Peter
authors.initials: P
authors.lastname: Thomsen
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020007:Implants, Experimental; D015847:Interleukin-4 / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects*; D013499:Surface Properties / Q000187:drug effects; D034421:Sus scrofa
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; C493709:RUNX2 protein, human; D015847:Interleukin-4; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase