| Budget Amount *help |
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Research Abstract |
Lipopolysaccharide (LPS) plays important roles on osteoclastic resorption of alveolar bone in periodontal disease. Although LPS stimulates osteoclastic bone resorption in vivo and in vitro, but its mechanism is not clear. Recently we showed that human umbilical cord blood and bone marrow cell cultures can adapted to form multinucleate cells (MNC's) that express an osteoclast, and we also suggested that the CFU-GM (colony forming unit-granulocyte macrophage) is the progenitor for the osteoclast In the present experiments, we studied the biological effect of LPS, an extracellular product from P gingivalis and E.coli , on the mechanism of osteoclast formation from CFU-GM-derived cells and on bone resorption. Addition of LPS (10-100 ng/ml) from either of P gingivalis and E.co/i to these cultures significantly increased the formation of 23C6-positive MINCs.Addition of anti-human IL-i to cultures treated with LPS totally inhibited the increase in MNC formation stimulated by either LPS.Both L
… More
PS's stimulated bone resorption, but the Porphyromonas gingivalis (Pgingivaris) LPS caused a 1.4 fold greater increase in the resorption area compared with the Escherihia coli (E.coli) one. The effects of LPS on regulation of tyrosine phosphorylation were also studied in experiments utilizing osteoclast precursor cells. The phosphorylation was detectable in LPS-treated CFU-GM cells and multinucleated cells. Also the phospholiration was detectable in border of each cells. When these cells were incubated with LPS from P gingivalis, a 42-kD protein band containing phoshotyrosine was detected. Addition of 100 nM herbimycin A to cultures treated with either LPS totally inhibited the bone resorption stimulated by Pgingivalis and K coli LPS's. However, herbimycin A did not inhibit the MNC formation. These experiments suggest that LPS stimulates osteoclast formation through a primary action on osteoclast precursor cells, which cells are induced by the action of IL- 1 produced by the LPS which in turn stimulates osteoclast formation, resulting in osteoclastic bone resorption. These findings also suggest that c-src kinase is involved in the regulation of bone-resorbing activity of osteoclasts by LPS. Less
|
