Lipopolysaccharides (LPS) induce the differentiation of human monocytes to osteoclasts in a tumour necrosis factor (TNF) alpha-dependent manner: a link between infection and pathological bone resorption.
The degradation of bone is a serious consequence of persistent bacterial infection, including periodontitis, infection-associated non-unions or osteomyelitis. To test the hypothesis that infection and inflammatory conditions promote the differentiation of monocytes to bone-resorbing osteoclasts, highly purified monocytes, or alternatively, cells of the promyeloid cell line U937, differentiated to monocyte-like cells, were cultivated in the presence of lipopolysaccharides (LPS) for up to 30 days. After 2-4 days, a massive aggregation of the cells was observed, after 15-20 days multinuclear cells with the morphological characteristics of osteoclasts became apparent. These cells expressed the osteoclast-typical proteins tartrate-resistant acid phosphate (TRAcP) and cathepsin K. Moreover, these cells formed resorption pits on calcium phosphate coated cover slips or ivory slices. To test whether the differentiation of the monocytes to osteoclast-like cells was mediated by tumour necrosis factor alpha (TNFalpha) secreted by the cells in culture, an antibody directed against TNFalpha was added together with LPS. Differentiation to osteoclast-like cells was inhibited, suggesting a paracrine effect of locally produced TNFalpha. In conclusion, we propose that local bacterial infections could create a microenvironment that promotes the generation of bone resorbing cells, which, in turn, could contribute to the infection-associated osteolysis.
Institut für Immunologie der Universität Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
Maik
M
Mörmann
Mareike
M
Thederan
Inaam
I
Nackchbandi
Thomas
T
Giese
Christof
C
Wagner
G Maria
GM
Hänsch
D000906:Antibodies / Q000494:pharmacology; D001850:Bone Diseases, Infectious / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D001862:Bone Resorption / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002469:Cell Separation; D006801:Humans; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*; D020298:U937 Cells
D000906:Antibodies; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha