Abstracts (complete list) - Wissenschaft Online

Maik Moermann, Mareike Thederan, Christof Wagner, Inaam Nakchbandi, Gertrud
Maria Hänsch
Differentiation of the promonocytic cell-line U 937 to
osteoclasts by bacterial lipopolysaccharides: a link between
infection and pathological bone resorption.
Bacterial biofilms formed on orthopaedic implants elicit persistent inflammation with
massive tissue destruction and osteolysis. To establish a link between infection and
osteolysis, we explored the possibility that bacterial infections promote the generation
of bone resorbing osteoclasts. In that context, the effect of bacterial lipopolysaccharides
(LPS) on the generation of osteoclasts was tested in vitro. Osteoclasts are derived from
haematopoietic cells, and differentiate to osteoclasts under the influence of signals
derived from stromal cells and/or T-lymphocytes. To exclude the effect of those cells,
the promonocytic cell line U937 was used. U937 were differentiated to monocytes by
use of phorbol ester, and then cultivated further with LPS. During culture U937 acquired
the LPS receptor CD14. As the culture progressed, expression of numerous monocytetypical
receptors, including CD11b, MHC class II, and CD 86 was induced, as were
osteoclast specific proteins like the tartrate resistant acid phosphatase (TRAP) and
cathepsin K. Furthermore, between days 4-6 by light microscopy a massive aggregation
of the cells was observed followed by cell fusion. By day 15 multinuclear cells with the
morphological characteristics of osteoclasts appeared. These cells were TRAP-positive
and able to degrade calcium phosphate coated on cover slips and ivory as well. Thus,
LPS as a single stimulus induces the differentiation of monocytes to cells with the
phenotypical and functional characteristics of osteoclasts generated by established
protocols. 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.