As a histone methyltransferase, enhancer of zeste homolog 2 (EZH2), suppresses osteoblast maturation and is involved in inflammation. However, the role of EZH2 in human periodontal ligament stem cells (PDLSCs) under inflammation still needs to be further investigated. This study aimed to identify the underlying mechanisms and explore the function of EZH2 in PDLSC osteogenesis under inflammation. PDLSCs were treated with sh-EZH2, DZNep or DKK1 under inflammation. The alkaline phosphatase (ALP) activity, alizarin red staining, and osteogenesis-related protein levels were analyzed. Lipopolysaccharide (LPS)-induced inflammation restrained osteogenic differentiation. Under inflammation, the upregulation of EZH2 suppressed the expression of osteogenic markers, including osteocalcin, runt-related transcription factor 2, and bone morphogenetic protein-2, the activity of ALP, and the accumulation of mineralization through the Wnt/β-catenin pathway. EZH2 knockdown inhibited the levels of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. These results suggested that LPS-induced overexpression of EZH2 suppressed PDLSC osteogenesis under inflammatory conditions through the Wnt/β-catenin pathway. These findings give new insights into the physiological differentiation and pathological inflammation of PDLSC osteogenesis, and provide an underlying therapeutic target for periodontitis.

中文翻译：

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靶向 EZH2 通过 Wnt/β-Catenin 通路改善 LPS 抑制的 PDLSC 成骨

作为组蛋白甲基转移酶，zeste 同源物 2 (EZH2) 的增强子，抑制成骨细胞成熟并参与炎症。然而，EZH2在炎症下人牙周膜干细胞（PDLSCs）中的作用仍有待进一步研究。本研究旨在确定炎症下 EZH2 在 PDLSC 成骨中的潜在机制并探索其功能。在炎症下用 sh-EZH2、DZNep 或 DKK1 处理 PDLSC。分析了碱性磷酸酶 (ALP) 活性、茜素红染色和成骨相关蛋白水平。脂多糖（LPS）诱导的炎症抑制成骨分化。在炎症条件下，EZH2 的上调抑制了成骨标志物的表达，包括骨钙素、runt 相关转录因子 2 和骨形态发生蛋白 2，ALP 的活性，以及​​通过 Wnt/β-catenin 途径积累的矿化。EZH2 敲低抑制了促炎细胞因子的水平，如白细胞介素 6 和肿瘤坏死因子-α。这些结果表明，LPS 诱导的 EZH2 过表达通过 Wnt/β-catenin 途径抑制炎症条件下的 PDLSC 成骨。这些发现为 PDLSC 成骨的生理分化和病理炎症提供了新的见解，并为牙周炎提供了潜在的治疗靶点。这些结果表明，LPS 诱导的 EZH2 过表达通过 Wnt/β-catenin 途径抑制炎症条件下的 PDLSC 成骨。这些发现为 PDLSC 成骨的生理分化和病理炎症提供了新的见解，并为牙周炎提供了潜在的治疗靶点。这些结果表明，LPS 诱导的 EZH2 过表达通过 Wnt/β-catenin 途径抑制炎症条件下的 PDLSC 成骨。这些发现为 PDLSC 成骨的生理分化和病理炎症提供了新的见解，并为牙周炎提供了潜在的治疗靶点。