The essential genes were identified by five AB patients for whole-exome sequencing and the microarray datasets GES38494 and GES132472. Moreover, the expression of key genes and their encoded proteins in AB tissues was explored. In addition, AB-derived the decellularized ECM (ABdECM) tissues were generated by the decellularization technique. Furthermore, the osteogenic development of periodontal ligament stem cells (PDLSCs) was mimicked by simulating the effects of the AB tumor microenvironment (TME).
The AB essential genes including COL1A2, COL4A2, FBN1, and HPSE were discovered. Among them, the expression of HPSE was down-regulated, while that of COL1A2, COL4A2, and FBN1 was noticeably upregulated in AB compared with normal gingival tissues of the jaws. In vitro osteogenic differentiation of PDLSCs was suppressed by the ABdECM.
Abnormal ECM proteins encoded by COL4A2, COL1A2, FBN1, and HPSE genes can cause disturbance in the ECM environment of AB and promote bone resorption.
方法:5名AB患者鉴定了必需基因,用于全外显子组测序和微阵列数据集GES38494和GES132472。此外,探讨了关键基因及其编码蛋白在AB组织中的表达。此外,通过脱细胞技术产生AB来源的脱细胞ECM(ABdECM)组织。此外,通过模拟AB肿瘤微环境(TME)的作用,模拟牙周膜干细胞(PDLSCs)的成骨发育。
结果:发现了AB必需基因,包括COL1A2、COL4A2、FBN1和HPSE。其中,HPSE的表达下调,与正常的颌骨牙龈组织相比,AB中的COL1A2,COL4A2和FBN1明显上调。ABdECM抑制了PDLSCs的体外成骨分化。
结论:由COL4A2,COL1A2,FBN1和HPSE基因编码的异常ECM蛋白可引起AB的ECM环境紊乱并促进骨吸收。