title: Prolonged exposure to bacterial toxins downregulated expression of toll-like receptors in mesenchymal stromal cell-derived osteoprogenitors.
abstract: BACKGROUND
  Human mesenchymal stromal cells (MSCs, also known as mesenchymal stem cells) are multipotent cells with potential therapeutic value. Owing to their osteogenic capability, MSCs may be clinically applied for facilitating osseointegration in dental implants or orthopedic repair of bony defect. However, whether wound infection or oral microflora may interfere with the growth and osteogenic differentiation of human MSCs remains unknown. This study investigated whether proliferation and osteogenic differentiation of MSCs would be affected by potent gram-positive and gram-negative derived bacterial toxins commonly found in human settings.
  
  
  RESULTS
  We selected lipopolysaccharide (LPS) from Escherichia coli and lipoteichoic acid (LTA) from Streptococcus pyogenes as our toxins of choice. Our findings showed both LPS and LTA did not affect MSC proliferation, but prolonged LPS challenge upregulated the osteogenic differentiation of MSCs, as assessed by alkaline phosphatase activity and calcium deposition. Because toll-like receptors (TLRs), in particularly TLR4 and TLR2, are important for the cellular responsiveness to LPS and LTA respectively, we evaluated their expression profiles serially from MSCs to osteoblasts by quantitative PCR. We found that during osteogenic differentiation, MSC-derived osteoprogenitors gradually expressed TLR2 and TLR4 by Day 12. But under prolonged incubation with LPS, MSC-derived osteoprogenitors had reduced TLR2 and TLR4 gene expression. This peculiar response to LPS suggests a possible adaptive mechanism when MSCs are subjected to continuous exposure with bacteria.
  
  
  CONCLUSIONS
  In conclusion, our findings support the potential of using human MSCs as a biological graft, even under a bacterial toxin-rich environment.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, The University of Hong Kong, Hong Kong, PR China. irene_hku@yahoo.com
authors.forename: Irene Fung Ying
authors.initials: IF
authors.lastname: Mo
authors.forename: Kevin Hak Kong
authors.initials: KH
authors.lastname: Yip
authors.forename: Wing Keung
authors.initials: WK
authors.lastname: Chan
authors.forename: Helen Ka Wai
authors.initials: HK
authors.lastname: Law
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Godfrey Chi Fung
authors.initials: GC
authors.lastname: Chan
mesh_terms: D001427:Bacterial Toxins / Q000494:pharmacology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D013682:Teichoic Acids / Q000737:chemistry / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C082161:lipopolysaccharide A; C009900:lipoteichoic acid
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