HOXA10 inhibit the osteogenic differentiation of periodontal ligament stem cells by regulating β-catenin localization and DKK1 expression
HOXA10 inhibit the osteogenic differentiation of periodontal ligament stem cells by regulating β-catenin localization and DKK1 expression
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HOXA10通过调节β-catenin定位和DKK1表达抑制牙周膜干细胞成骨分化
DOI：
10.1080/03008207.2020.1756271
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发表时间：
2020-04-26
影响因子：
2.9
通讯作者：
Yang, Guoli
中科院分区：
文献类型：
--
作者：
Wang, Chengze;Li, Yongzheng;Yang, Guoli
简介：人牙周膜干细胞（hPDLSCs）是在牙齿牙周膜附近发现的干细胞。在正畸治疗和慢性牙周炎的过程中，牙周膜和牙槽骨的再生与这些纤维有关。目的：同源异型盒基因HOXA 10调控干细胞的成骨分化。然而，HOXA 10在hPDLSC中的作用仍不清楚。因此，我们在体外研究HOXA 10对人PDLSC成骨分化的影响。方法：首先分离hPDLSCs并鉴定其生物学特性。其次，我们评估了HOXA 10的过表达和敲低对PDLSC成骨分化的影响。最后，使用特异性Wnt信号通路激活剂氯化锂（LiCl）和抑制剂ICG-001来研究Wnt信号通路在HOXA 10诱导的成骨分化调节中的参与。结果如下：ALP和茜素红染色显示，过表达HOXA 10抑制PDLSC体外成骨分化，而HOXA 10敲除则表现出相反的效果。HOXA 10负调节细胞核β-连环蛋白和成骨分化标志物，包括碱性磷酸酶（ALPL）和整合素结合唾液蛋白（IBSP）。上调HOXA 10减少了细胞核β-连环蛋白，增加了DKK 1的表达。然而，HOXA 10敲低增强了细胞核β-连环蛋白的积累并降低了DKK 1的表达。Wnt/β-连环蛋白通路激活剂LiCl可恢复HOXA 10过表达对成骨分化的这些负面影响。HOXA 10基因敲减后的成骨分化作用可被Wnt通路抑制剂ICG-001所拮抗。结论：这些数据表明HOXA 10通过调节β-连环蛋白定位和DKK 1抑制牙周膜干细胞的成骨分化。
Introduction: Human periodontal ligament stem cells (hPDLSCs) are stem cells found near the tooth periodontal ligament. These cels are involved in the regeneration of the periodontal ligament and alveolar bone during orthodontic treatment and chronic periodontitis. Objectives: The Homeobox gene HOXA10 regulates the osteogenic differentiation of stem cells. However, the role of HOXA10 in hPDLSCs remains unclear. Therefore, we studied the effects of HOXA10 on human PDLSC osteogenic differentiation in vitro. Methods: First, hPDLSCs were isolated and characterized. Second, we assessed the effects of overexpression and knockdown of HOXA10 on PDLSC osteogenic differentiation. Finally, the specific Wnt signaling pathway activator lithium chloride (LiCl) and inhibitor ICG-001 were used to investigate the involvement of the Wnt signaling pathway in HOXA10-induced regulation of osteogenic differentiation. Results: Overexpressing HOXA10 inhibited PDLSC osteogenic differentiation in vitro, shown by ALP and Alizarin Red staining, while HOXA10 knockdown demonstrated the opposite effects. HOXA10 negatively regulated nuclear beta-catenin and osteogenic differentiation markers including alkaline phosphatase (ALPL) and integrin-binding sialoprotein (IBSP). Upregulating HOXA10 reduced nuclear beta-catenin and increased DKK1 expression. However, HOXA10 knockdown enhanced nuclear beta-catenin accumulation and reduced DKK1 expression. These negative effects on osteogenic differentiation by HOXA10 overexpression were restored by the Wnt/beta-catenin pathway activator LiCl. The increased osteogenic differentiation effects of HOXA10 knockdown were antagonized by ICG-001, a Wnt pathway inhibitor. Conclusion: These data demonstrate that HOXA10 inhibits the osteogenic differentiation of periodontal ligament stem cells by regulating beta-catenin localization and DKK1.