The involvement of platelet-derived growth factor receptors and insulin-like growth factor-I receptors signaling during mineralized nodule formation by human periodontal ligament cells.
The involvement of platelet-derived growth factor receptors and insulin-like growth factor-I receptors signaling during mineralized nodule formation by human periodontal ligament cells.
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DOI：
10.1111/j.1600-0765.2004.00750.x
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发表时间：
2004-12
影响因子：
3.5
通讯作者：
E. Nemoto;M. Shimonishi;Y. Nitta;H. Shimauchi
中科院分区：
文献类型：
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作者：
E. Nemoto;M. Shimonishi;Y. Nitta;H. Shimauchi
背景与目的牙周膜细胞被认为具有向成牙骨质细胞或成骨细胞分化的能力，并能在体外形成矿化结节。然而，确切的机制尚不清楚。在此，我们探讨了生长因子受体，如血小板衍生生长因子受体(PDGFR)、胰岛素样生长因子-I受体(IGF-IR)和表皮生长因子受体(EGFR)在牙周膜细胞及其配体体外分化过程中的可能作用。方法人牙周膜细胞在地塞米松、抗坏血酸和β-甘油磷酸存在下诱导分化形成矿化结节，von Kossa染色鉴定。用流式细胞仪/逆转录聚合酶链式反应分析受体及其配体的表达。结果在分化过程中，PDGFR-α维持在较低水平。然而，当矿化结核形成时，PDGFR-β保持在略高的水平，与对照水平相反。相反，IGF-IR和EGFR与对照组没有显著差异。PDGFR激酶阻滞剂(AG1295和AG1296)强烈抑制矿化结节的形成，IGF-IR激酶阻滞剂(I-Ome-AG538和AG1024)部分抑制矿化结节的形成，而EGFR激酶阻滞剂(AG99)不抑制矿化结节的形成。在矿化结节形成过程中，PDGF-A、PDGF-C、PDGF-D、IGF-I和IGF-II在对照组和地塞米松/抗坏血酸处理组的牙周膜细胞上均有表达，但表达模式不同。结论牙周膜细胞上的PDGFs/PDGFR和IGFS/IGF-IR途径参与了矿化结节的形成，牙周膜细胞表达的PDGFs和IGFS可能参与了矿化结节的形成。
BACKGROUND AND OBJECTIVE Periodontal ligament cells are regarded to have the capacity to differentiate into cementoblasts or osteoblasts, and are capable of forming a mineralized nodule in vitro. However, the precise mechanisms are unclear. Here we evaluated the possible involvement of growth factor receptors, such as the platelet-derived growth factor receptor (PDGFR), insulin-like growth factor-I receptor (IGF-IR), and epidermal growth factor receptor (EGFR) on periodontal ligament cells and their ligands during periodontal ligament cells differentiation in vitro. METHODS Human periodontal ligament cells were differentiated via culturing in the presence of dexamethasone, ascorbic acid, and beta-glycerophosphate for mineralized nodule formation, characterized by von Kossa staining. Expressions of receptors and their ligands were analyzed by flow cytometry/reverse transcription-polymerase chain reaction. RESULTS During the differentiation, PDGFR-alpha was held at a lower level compared with the control. PDGFR-beta, however, was maintained at a slightly higher level that was reversed to the control level when mineralized nodules formed. In contrast, IGF-IR and EGFR were not substantially different from the control. The mineralized nodule formation was strongly inhibited by a PDGFR kinase blocker (AG1295 and AG1296), partially inhibited by an IGF-IR kinase blocker (I-Ome-AG538 and AG1024), and not inhibited by an EGFR kinase blocker (AG99). PDGF-A, PDGF-C, PDGF-D, IGF-I, and IGF-II, but not PDGF-B, were expressed on the control as well as dexamethasone/ascorbic acid-treated periodontal ligament cells during mineralized nodule formation; however, the pattern of their expressions was quite different. CONCLUSION These findings suggest that a pathway of PDGFs/PDGFR and IGFs/IGF-IR on periodontal ligament cells are involved during mineralized nodule formation, and that PDGFs and IGFs expressed by periodontal ligament cells may contribute to the formation.