PTHrP Induces Notch Signaling in Periodontal Ligament Cells
PTHrP Induces Notch Signaling in Periodontal Ligament Cells
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DOI：
10.1177/0022034509337899
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发表时间：
2009-06-01
影响因子：
7.6
通讯作者：
Okabe, K.
中科院分区：
文献类型：
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作者：
Nakao, A.;Kajiya, H.;Okabe, K.
牙周膜(PDL)细胞在牙萌出和牙槽骨代谢中起重要作用。我们之前曾报道，PTHrP增加了人PDL细胞中RANKL的表达，表明它促进了牙齿萌出过程中破牙细胞性牙根的吸收。虽然已知Notch相关基因在骨发育中起关键作用，但Notch信号通路在PDL细胞中在牙齿和骨吸收中的作用尚不清楚。我们假设PTHrP在PDL细胞中诱导一种Notch配体，从而调节成骨和破牙发生。我们发现PTHrP以剂量和时间依赖的方式增加人PDL细胞Notch1配体Jagged1的表达。PTHrP诱导的Jagged1上调是由PKA激活介导的，而不是由PKC介导的。Jagged1还促进RANKL诱导的破骨细胞生成。这些结果表明，PTHrP诱导PDL细胞表达Jagged1，导致成骨和破牙分化，从而可能促进牙齿和牙槽骨的吸收。
Periodontal ligament (PDL) cells are known to play important roles in tooth eruption and alveolar bone metabolism. We previously reported that PTHrP increases RANKL expression in human PDL cells, suggesting that it promotes odontoclastic root resorption during tooth eruption. While it is known that Notch-related genes play a key role during bone development, the role of the Notch signaling pathway in PDL cells during tooth and bone resorption is less clear. We hypothesized that PTHrP induces a Notch ligand in PDL cells and thereby regulates osteo-and odontoclastogenesis. We found that PTHrP increased Notch1 ligand Jagged1 expression in human PDL cells in a dose-and time-dependent manner. PTHrP-induced Jagged1 up-regulation was mediated by PKA activation, but not by PKC. Jagged1 also promoted RANKL-induced osteoclastogenesis. These results demonstrate that PTHrP induces Jagged1 expression in PDL cells, leading to osteo-and odontoclastogenesis, and thus likely promoting tooth and alveolar bone resorption.