Thammasitboon Kewalin, Goldring Steven R, Boch Jason A
Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Bone. 2006 Jun;38(6):845-52. doi: 10.1016/j.bone.2005.10.013. Epub 2005 Dec 27.
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-alpha 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-alpha 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.
在根尖周病变和牙周疾病中，细菌入侵会导致慢性炎症，进而破坏牙周韧带的结构完整性，并导致牙槽骨进行性破坏。这些病症的发病机制不仅归因于细菌诱导的组织破坏，还归因于牙周组织修复缺陷。积累的数据还表明，脂多糖（LPS）可直接诱导多种细胞类型发生细胞死亡或凋亡，包括巨噬细胞、成骨细胞、血管内皮细胞、肝细胞和心肌细胞。本研究假设，细菌LPS诱导成骨细胞和牙周韧带成纤维细胞（PDL细胞）凋亡是牙周和根尖周疾病中牙周组织修复缺陷的一个重要促成因素。已表明巨噬细胞通过增加促炎细胞因子的产生来对细菌LPS作出反应。此外，在发炎的牙周组织中存在大量巨噬细胞。我们推测巨噬细胞是介导成骨细胞和PDL细胞响应细菌衍生LPS而发生凋亡的潜在候选细胞。用LPS刺激巨噬细胞样细胞系RAW 264.7，并使用条件培养基处理成骨细胞和PDL细胞。细菌LPS对小鼠成骨细胞或PDL细胞没有直接的凋亡作用，而来自LPS激活的巨噬细胞的条件培养基能够诱导这些细胞凋亡。为了评估巨噬细胞释放的肿瘤坏死因子-α（TNF-α）对成骨细胞和PDL细胞凋亡的作用，在存在和不存在抗TNF-α中和抗体的情况下，将细胞与来自LPS处理的巨噬细胞的条件培养基一起孵育。TNF-α中和抗体预处理以剂量依赖性方式抑制来自LPS处理的巨噬细胞的条件培养基对成骨细胞和PDL细胞凋亡的作用。这些结果表明，LPS可通过诱导巨噬细胞释放TNF-α间接诱导成骨细胞和PDL细胞凋亡。这些研究为细菌衍生的LPS可能导致牙周和根尖周疾病中牙周和骨组织修复缺陷的潜在机制提供了见解。
