Characterization of bone-resorbing activity in human periapical lesions.

Characterization of bone-resorbing activity in human periapical lesions.
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DOI:
10.1016/s0099-2399(06)80503-0
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发表时间:
1993-03
影响因子:
4.2
通讯作者:
C. Y. Wang;P. Stashenko
C. Y. Wang;P. Stashenko
中科院分区:
医学2区
文献类型:
--
作者:
C. Y. Wang;P. Stashenko

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对人根尖周肉芽肿提取物进行骨吸收活性检测。所有肉芽肿(10/10)均含有低水平但显著的骨吸收活性,范围为2.1 - 4.9%处理- %对照/mg特异性45 Ca释放,通过胎鼠长骨测定法测定。健康的牙周膜和牙髓没有明显的吸收活性。在表征研究中,提取物合并液中的再吸收活性不受多粘菌素B的影响,表明其活性部分与脂多糖不同。再吸收活性也不受加热至56°C持续30分钟的影响,但通过蛋白酶K处理或加热至70°C完全消除,表明活性主要是蛋白质介导的。快速高效液相色谱凝胶过滤研究表明,活性可分离为两个主峰,Mr 30,000 - 60,000(I)和15,000 - 20,000(II),以及一个小于1,000(III)的次峰。峰III经放射免疫法鉴定为前列腺素E2。在抑制研究中,几乎所有存在的再吸收活性均被抗白细胞介素1β(69%)和抗肿瘤坏死因子β(66%)抗血清抑制,而抗白细胞介素1α和抗肿瘤坏死因子α无影响。用环氧化酶抑制剂吲哚美辛治疗也使活性降低了74%。总之,这些数据表明,慢性人类根尖周病变中存在的大多数骨吸收活性可归因于吸收细胞因子白细胞介素1β和肿瘤坏死因子β的作用,通过吲哚美辛依赖性和非依赖性途径发挥作用。这种活动可能会起到防止修复性骨形成的作用,在面对根管系统内的持续感染。
Extracts of human periapical granulomas were tested for the presence of bone-resorbing activity. All granulomas (10 of 10) contained low but significant levels of bone-resorbing activity, ranging from 2.1 to 4.9% treatment — % control/mg specific45Ca release, as determined by the fetal rat long bone assay. Healthy periodontal ligament and dental pulp had no significant resorbing activity. In characterization studies, the resorbing activity in an extract pool was unaffected by the presence of polymyxin B, indicating an active moiety distinct from lipopolysaccharide. Resorbing activity was also unaffected by heating to 56°C for 30 min, but was completely abolished by proteinase K treatment or heating to 70°C, indicating that activity was largely protein mediated. Fast performance liquid chromatography gel filtration studies demonstrated that activity could be resolved to two major peaks, ofMr30,000 to 60,000 (I), and 15,000 to 20,000 (II), with a minor peak present at <1,000 (III). Peak III was identified as prostaglandin E2by radioimmunoassay. In inhibition studies, virtually all of the resorbing activity present was inhibited by anti-interleukin 1β (69%) and anti-tumor necrosis factor β (66%) antisera, whereas anti-interleukin 1α and antitumor necrosis factor α had no effect. Treatment with the cycloxygenase inhibitor indomethacin also reduced activity by 74%. Taken together, these data demonstrate that most bone-resorbing activity present in chronic human periapical lesions is attributable to the action of resorptive cytokines interleukin 1β and tumor necrosis factor β, acting via both indomethacin-dependent and independent pathways. This activity may function to prevent reparative bone formation in the face of ongoing infection within the root canal system.