期刊
BONE
卷 38, 期 6, 页码 845-852出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2005.10.013
关键词
apoptosis; osteoblasts; bone resorption; alveolar bone; bone repair
资金
- NIAMS NIH HHS [R01-AR047665] Funding Source: Medline
- NIDCR NIH HHS [K22-DE14197] Funding Source: Medline
- NIDDK NIH HHS [R01-DK46773] Funding Source: Medline
In periradicular lesions and periodontal disease, bacterial invasion leads to chronic inflammation resulting in disruption of the structural integrity of the periodontal ligament and progressive alveolar bone destruction. The pathogenesis of these conditions has been attributed not only to bacterial-induced tissue destruction but also to a defect in periodontal tissue repair. Accumulated data have also shown that lipopolysaccharide (LPS) can directly induce cell death or apoptosis in many cell types, including macrophages, osteoblasts, vascular endothelial cells, hepatocytes and myocytes. The present study hypothesized that bacterial LPS-induced apoptosis in osteoblasts and periodontal ligament fibroblasts (PDL cells) is an important contributing factor to the defect in periodontal tissue repair in periodontal and periapical disease. Macrophages have been shown to respond to bacterial LPS by increasing the production of proinflammatory cytokines. In addition, large numbers of macrophages are present in inflamed periodontal tissue. We speculated that macrophages were a potential candidate cell for mediating apoptosis in osteoblasts and PDL cells in response to bacteria-derived LPS. The macrophage-like cell line, RAW 264.7, was stimulated with LPS, and the conditioned medium was used to treat osteoblasts and PDL cells. Bacterial LPS had no direct apoptotic effect on mouse osteoblasts or PDL cells, whereas the conditioned medium from LPS-activated macrophages was able to induce apoptosis in these cells. To evaluate the contribution of tumor necrosis factor-alpha (TNF-alpha) released from macrophages on osteoblast and PDL cell apoptosis, cells were incubated with conditioned medium from LPS-treated macrophages in the presence and absence of anti-TNF-alpha neutralizing antibodies. TNF-a neutralizing antibody pretreatment inhibited the effect of conditioned medium from LPS-treated macrophages on osteoblast and PDL cell apoptosis in a dose-dependent manner. These results suggest that LPS could indirectly induce apoptosis in osteoblasts and PDL cells through the induction of TNF-a release from macrophages. These studies provide insight into a potential mechanism by which bacterial-derived LPS could contribute to defective periodontal and bone tissue repair in periodontal and periapical disease. (c) 2005 Elsevier Inc. All rights reserved.
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