Lipopolysaccharides (LPS) induce the differentiation of human monocytes to osteoclasts in a tumour necrosis factor (TNF) α-dependent manner: A link between infection and pathological bone resorp
- 作者：Maik Mö ; rmann ; Mareike Thederan ; Inaam Nackchb ; i ; Thomas Giese ; Christof Wagner ; G. Maria Hä ; nsch
- 关键词：Osteoclasts ; Monocytes ; LPS ; TNF
//www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0"> ; Bone infection ; Bone resorption ; U937
- 刊名：Molecular Immunology
- 出版年：2008
- 期刊代码：112_01615890
- 类别：bio
- 出版时间：July 2008
- 卷：45
- 期：12
- 页码：3330-3337
- 文件大小：849 K
摘要
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 
(TNF) secreted by the cells in culture, an antibody directed against TNF was added together with LPS. Differentiation to osteoclast-like cells was inhibited, suggesting a paracrine effect of locally produced TNF. 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.
(TNF) secreted by the cells in culture, an antibody directed against TNF was added together with LPS. Differentiation to osteoclast-like cells was inhibited, suggesting a paracrine effect of locally produced TNF. 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.