engleski

Lipopolysaccharide induces increased bone resorption by stimulating homing of osteoclast progenitors to the periosteal bone surface

Lipopolysaccharide (LPS) from gram-negative bacteria may cause chronic inflammation and subsequent bone loss, and has been involved in the pathogenesis of several bacterially induced bone diseases. LPS strongly stimulates osteoclast formation and induces production of many local pro-inflammatory factors. We investigated the effects of LPS on osteoclast differentiation in bone. C57BL/6 mice were injected during 4 weeks in a dose of 10 µ g LPS/g body weight and sacrificed at different time-points. Cells from different tissue sources (bone marrow, homogenized bone shafts, spleen and peripheral blood) were cultured with RANKL and M-CSF to stimulate osteoclast differentiation. Osteoclasts were detected as TRAP (tartarate resistant acid phosphatase) positive cells with three or more nuclei per cell. At week three after LPS stimulation, number of differentiated osteoclasts cultured from cells extracted from bone shafts was higher in LPS-treated mice compared with control mice. This was in correlation to the decrease in bone volume and trabecular thickness detected by micro-CT. In addition, histological slices of femurs indicated that LPS injection altered bone metabolism in vivo by inducing increased osteoresorption in bone started from periosteal bone surface. This osteoresorptive effect of LPS in bone cortex was confirmed by gene expression analysis by quantitative PCR, which showed increased expression of osteoclast differentiation genes including RANK and cFMS. We concluded that LPS strongly supports osteoclast differentiation and our further aim is to elucidate the origin of osteoclast precursor cells that mediate increased bone resorption in our model.

lipopolysaccharide ; osteoclasts ; resorption ; inflammation

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