APOPTOSIS OF OSTEOCLASTS AND INFLAMMATORY BONE

牙周炎往往导致牙齿脱落，由于炎症性骨吸收。骨吸收是由破骨细胞介导的。虽然目前对破骨细胞的分化途径尚不清楚，但已知多种炎症介质可触发破骨细胞的产生。我们在体外实验中发现各种牙周细菌的脂多糖（LPS）介导破骨细胞的形成并刺激骨吸收。在这个项目中，我们研究了LPS介导的牙周细菌放线菌的破骨细胞分化机制。在小鼠骨髓培养中，放线菌胞杆菌LPS诱导破骨细胞形成。吲哚美辛和抗IL-1抗体明显抑制破骨细胞的形成，提示前列腺素E2 （PGE2）和IL-1参与了lps介导的破骨细胞形成。我们还发现放线菌脂多糖诱导成骨细胞分化因子（ODF）在成骨细胞谱系上的表达。这些结果表明，放线菌脂多糖通过上调牙周组织中PGE2、IL-1和ODF介导破骨细胞的形成。此外，我们发现牛磺酸（一种含硫氨基酸）抑制了a .放线菌comitans LPS介导的破骨细胞形成。牛磺酸也被发现抑制结扎介导的仓鼠牙周炎的实验性骨吸收。

Periodontitis often results in tooth loss due to inflammatory bone resorption. Bone resorption is mediated by osteoclasts. Although the differentiation pathway of osteoclasts is not well known at present, various inflammatory mediators are known to trigger the production of osteoclasts. We have found that lipopolysaccharides (LPS) of various periodontophatic bacteria mediate osteoclast formation and stimulate bone resorption in vitro. In this project, we investigate the mechanism of osteoclast differentiation mediated by LPS from a periodontophatic bacteria Actinobacillus actinomycetemcomitans.In mouse bone marrow cultures, LPS of A. actinomycetemocomitans induced osteoclast formation. Indomethacin and anti-IL-1 antibodies significantly inhibited the osteoclast formation, suggesting that prostaglandin E2 (PGE2) and IL-1 were involved in LPS-mediated osteoclast formation. We also found that LPS from A. actinomycetemcomitans induced expression of osteoclast differentiation factor (ODF) on cells of osteoblastic lineage. These results indicated that LPS of A. actinomycetemcomitans mediated osteoclast formation through upregulation of PGE2, IL-1 and ODF in periodontal tissues. Furthermore, we found that taurine, a sulfer containing amino acid, inhibited the osteoclast formation mediated by LPS from A. actinomycetemcomitans. Taurine was also found to inhibit the experimental bone resorption in ligature-mediated periodontitis in hamsters.