赖氨酸乙酰基转移酶2A通过经典Wnt通路影响牙周膜干细胞成骨分化

目的 探讨赖氨酸乙酰基转移酶2A（KAT2A）调控牙周膜干细胞（PDLSCs）成骨分化的机制。方法 分离培养来自健康志愿者的PDLSCs（H-PDLSCs）和牙周炎患者的PDLSCs（P-PDLSCs）,比较传代细胞中KAT2A基因的表达水平。采用KAT2A基因干扰H-PDLSCs,检测KAT2A基因干扰对H-PDLSCs成骨分化的影响;同时检测KAT2A干扰后对经典Wnt通路及其配体的影响,确定KAT2A基因与经典Wnt通路的上下游关系。结果 与H-PDLSCs相比,P-PDLSCs中KAT2A基因的表达下降,差异有统计学意义（P<0.05）。KAT2A基因被干扰后,PDLSCs成骨能力下降（P<0.05）,同时经典Wnt通路被激活,拮抗剂Dickkopf-1（DKK-1）表达下调;加入DKK-1后,被干扰的PDLSCs成骨分化功能恢复,而KAT2A的表达不受影响,仍维持较低水平。结论 牙周炎可导致PDLSCs中KAT2A基因表达下降,激活经典Wnt通路,抑制细胞的成骨分化。

K (lysine) acetyltransferase 2A affects the osteogenic differentiation of periodontal ligament stem cells through the canonical Wnt pathway

Objective This study aims to investigate the mechanism of K (lysine) acetyltransferase 2A (KAT2A) regulation and control on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Methods The expression levels of KAT2A in PDLSCs were compared from each generation of the normal (H-PDLSCs) and periodontitis tissues (P-PDLSCs). The influences of KAT2A gene interference on the osteogenic differentiation of PDLSCs were also detected. In addition, the influences of the KAT2A gene interference to the canonical Wnt pathway and ligands were detected. The upstream and down-stream relationships between KAT2A and canonical Wnt pathway were also determined. Results The decreased expression of KAT2A in PDLSCs from the inflammatory tissue in each generation was compared with that in PDLSCs from the healthy tissue, and the difference was statistically significant (P<0.05). When the KAT2A gene was disrupted, the osteogenesis ability of PDLSC was declined, and the difference was statistically significant (P<0.05). The canonical Wnt pathway was activated, and the antagonist Dickkopf-1 (DKK-1) was reduced. After the DKK-1 addition, the osteogenic differentiation of the disturbed PDLSCs was recovered, and KAT2A was unaffected. Conclusion The KAT2A expression in PDLSCs was decreased because of perio-dontitis. The classical Wnt pathway was activated to inhibit the osteogenic differentiation of the cells.