Effects of TNF-α on Cementoblast Differentiation, Mineralization, and Apoptosis
Effects of TNF-α on Cementoblast Differentiation, Mineralization, and Apoptosis
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TNF-α 对成牙骨质细胞分化、矿化和细胞凋亡的影响
DOI：
10.1177/0022034515590349
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发表时间：
2015-09-01
影响因子：
7.6
通讯作者：
Huo, F. Y.
中科院分区：
文献类型：
--
作者：
Wang, Y. L.;He, H.;Huo, F. Y.
肿瘤坏死因子-α（TNF-α）参与各种炎症过程，包括牙周炎。虽然TNF-α对牙周膜成纤维细胞和成骨细胞的影响已被广泛报道，但其对牙骨质生成细胞（负责牙骨质生成的细胞）的影响仍不清楚。在这项研究中，我们发现TNF-α通过抑制分化和诱导凋亡抑制成牙骨质细胞的矿化能力。在此过程中，多种信号通路，如p53、PP 2A（C）、p38、Erk 1/2、JNK、PI 3 K-Akt和NF-κ B B被激活。使用特异性抑制剂和siRNA转染证实，TNF-α对成牙骨质细胞分化和凋亡的影响通过抑制p53活性而部分消除。相比之下，TNF-α的作用甚至因抑制p38、Erk 1/2、JNK、PI 3 K-Akt和NF-κ B途径而加剧。此外，通过阻断p38、Erk 1/2、JNK和PI 3 K-Akt信号通路，p53活性进一步增强。这些结果表明TNF-α诱导的成牙骨质细胞分化抑制和凋亡部分依赖于p53活性。p38、Erk 1/2、JNK、PI 3 K-Akt和NF-κ B通路也被激活，但作为平衡参与者限制而不是传导TNF-α的负面作用。除了NF-κ B通路外，这些平衡作用依赖于或至少部分依赖于p53。
Tumor necrosis factor-alpha (TNF-alpha) is involved in various inflammatory processes, including periodontitis. Although the influences of TNF-alpha on periodontal ligament fibroblasts and osteoblasts have been widely documented, its effects on cementoblasts, the cells responsible for cementum production, remain largely unknown. In this study, we found that TNF-alpha suppressed the mineralization ability of cementoblasts by inhibiting differentiation and inducing apoptosis. Various signaling pathways, such as p53, PP2A(C), p38, Erk1/2, JNK, PI3K-Akt, and NF-kappa B, were activated during this process. The use of a specific inhibitor and siRNA transfection confirmed that the effects of TNF-alpha on differentiation and apoptosis in cementoblasts were partially abrogated by inhibiting p53 activity. By contrast, the effects of TNF-alpha were even exacerbated by the inhibition of the p38, Erk1/2, JNK, PI3K-Akt, and NF-kappa B pathways. Moreover, p53 activity was further enhanced by blocking the p38, Erk1/2, JNK, and PI3K-Akt signaling pathways. Taken together, these results suggested that the differentiation inhibition and apoptosis in cementoblasts induced by TNF-alpha were partially dependent on p53 activity. The p38, Erk1/2, JNK, PI3K-Akt, and NF-kappa B pathways were also activated but acted as balancing players to limit rather than conduct the negative effects of TNF-alpha. These balancing effects were dependent, or at least partially dependent, on p53, except for the NF-kappa B pathway.