title: Lipopolysaccharide induces proliferation and osteogenic differentiation of adipose-derived mesenchymal stromal cells in vitro via TLR4 activation.
abstract: Multipotent mesenchymal stromal cells (MSC) are capable of multi-lineage differentiation and support regenerative processes. In bacterial infections, resident MSC can come intocontact with and need to react to bacterial components. Lipopolysaccharide (LPS), a typical structure of Gram-negative bacteria, increases the proliferation and osteogenic differentiation of MSC. LPS is usually recognized by the toll-like receptor (TLR) 4 and induces pro-inflammatory reactions in numerous cell types. In this study, we quantified the protein expression of TLR4 and CD14 on adipose-derived MSC (adMSC) in osteogenic differentiation and investigated the effect of TLR4 activation by LPS on NF-κB activation, proliferation and osteogenic differentiation of adMSC. We found that TLR4 is expressed on adMSC whereas CD14 is not, and that osteogenic differentiation induced an increase of the amount of TLR4 protein whereas LPS stimulation did not. Moreover, we could show that NF-κB activation via TLR4 occurs upon LPS treatment. Furthermore, we were able to show that competitive inhibition of TLR4 completely abolished the stimulatory effect of LPS on the proliferation and osteogenic differentiation of adMSC. In addition, the inhibition of TLR4 leads to the complete absence of osteogenic differentiation of adMSC, even when osteogenically stimulated. Thus, we conclude that LPS induces proliferation and osteogenic differentiation of adMSC in vitro through the activation of TLR4 and that the TLR4 receptor seems to play a role during osteogenic differentiation of adMSC.
authors.affiliation: Department of Cell Biology, University Medicine Rostock, Schillingallee 69, D-18057 Rostock, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Herzmann
authors.affiliation: Department of Cell Biology, University Medicine Rostock, Schillingallee 69, D-18057 Rostock, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Salamon
authors.affiliation: Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Schillingallee 70, D-18057 Rostock, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Fiedler
authors.affiliation: Department of Cell Biology, University Medicine Rostock, Schillingallee 69, D-18057 Rostock, Germany. Electronic address: kirsten.peters@med.uni-rostock.de.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Peters
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Adipose-derived mesenchymal stromal cells (adMSC); Lipopolysaccharide (LPS); Osteogenic differentiation; Proliferation; Toll-like receptor 4 (TLR4)