Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory, Sun Yat-Sen University, Guangzhou, China.
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China.
J Oral Pathol Med. 2018 Oct;47(9):836-846. doi: 10.1111/jop.12761. Epub 2018 Jul 27.
The process of marsupialization involves the release of intracystic pressure and the fluid contained within. Marsupialization of cystic ameloblastoma is controversial; therefore, we investigated how hydrostatic pressure influences biological behaviours of ameloblastoma cells and its underlying mechanisms.
An ameloblastoma epithelial cell line, hTERT -AM, was exposed to different hydrostatic pressures with or without Dickkopf-related protein 1 (also known as DKK), a canonical Wnt signalling pathway inhibitor. A CCK-8 assay, a monolayer wound assay, and a Transwell assay were used to determine cell proliferation, migration and invasion, respectively. qRT-PCR and Western blot were used to detect expression of MMP-2, MMP-9, RANKL and other downstream targets of Wnt signalling.
Elevated hydrostatic pressure promoted migration and invasion of ameloblastoma cells, but inhibited proliferation. Expression of MMP-2, MMP-9, LEF-1, cyclin D1, c-Jun and c-Myc was significantly upregulated under elevated hydrostatic pressure, and these effects could be abolished by DKK1. Expression of RANKL, which is thought to be a downstream target of Wnt signalling, did not significantly change under elevated hydrostatic pressure.
This study indicates that elevated hydrostatic pressure promotes the migration and invasion of ameloblastoma cells by activating the Wnt/β-catenin pathway, thereby increasing expression of MMP-2, MMP-9 and other Wnt signalling downstream targets. This suggests that marsupialization may reduce invasiveness and reverse the bone resorption process by lowering intracystic hydrostatic pressure in cystic ameloblastoma.
囊内切开术涉及囊内压力和内含物的释放。 囊性成釉细胞瘤的囊内切开术存在争议； 因此，我们研究了静水压力如何影响成釉细胞瘤细胞的生物学行为及其潜在机制。
将成釉细胞瘤上皮细胞系 hTERT-AM 暴露于不同的静水压力下，同时或不使用 Dickkopf 相关蛋白 1（也称为 DKK），一种经典的 Wnt 信号通路抑制剂。CCK-8 测定、单层划痕测定和 Transwell 测定分别用于测定细胞增殖、迁移和侵袭。qRT-PCR 和 Western blot 用于检测 MMP-2、MMP-9、RANKL 和 Wnt 信号下游其他靶标的表达。
升高的静水压力促进了成釉细胞瘤细胞的迁移和侵袭，但抑制了增殖。在升高的静水压力下，MMP-2、MMP-9、LEF-1、cyclin D1、c-Jun 和 c-Myc 的表达明显上调，而 DKK1 可以消除这些作用。被认为是 Wnt 信号下游靶标的 RANKL 的表达在升高的静水压力下没有明显变化。
本研究表明，升高的静水压力通过激活 Wnt/β-catenin 通路促进成釉细胞瘤细胞的迁移和侵袭，从而增加 MMP-2、MMP-9 和其他 Wnt 信号下游靶标的表达。这表明囊内切开术通过降低囊性成釉细胞瘤囊内的静水压力可能降低侵袭性并逆转骨质吸收过程。
