Ding Jiaqi, Dong Kai, Niu Delong, Qiu Wenjie, Zhou Wenjuan, Liu Zhonghao
The Affiliated Yantai Stomatological Hospital, Binzhou Medical University, Yantai 264000, China.
Yantai Engineering Research Center for Digital Technology of Stomatology, Yantai 264000, China.
Int J Dent. 2025 Aug 15;2025:5566776. doi: 10.1155/ijod/5566776. eCollection 2025.
High glucose (HG)-induced oxidative stress affects implant osseointegration through various pathways. Oxidative stress is widely recognized to suppress the Wnt/β-catenin signaling pathway, thereby impairing bone metabolism and homeostasis. However, there are few reports on whether excessive reactive oxygen species (ROS) influence osteogenic differentiation of stem cells via the noncanonical Wnt/calmodulin-dependent protein kinase II (CaMK II) pathway. An investigation of the mechanism by which ROS/CaMK II/β-catenin signaling axis influences the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on titanium surfaces is being carried out in this investigation. In this study, titanium plates were specially treated to simulate implant surfaces. An osteogenic medium containing HG was used to cultivate BMSCs on titanium surfaces. The effects of excessive ROS induced by HG on the osteogenic differentiation of BMSCs, as well as on the expression of β-catenin and CaMK II, were examined using methods such as alkaline phosphatase (ALP) activity assay, quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. Additionally, the effects of the Wnt/β-catenin and Wnt/CaMK II pathways on the osteogenesis of BMSCs on the titanium surface were observed by separately adding activators or inhibitors of β-catenin and CaMK II. Excessive ROS induced by HG inhibited osteogenic differentiation. In a HG environment, β-catenin expression decreased, while CaMK II expression increased. Moreover, we observed that activation of the Wnt/β-catenin pathway promoted osteogenesis, whereas activation of the Wnt/CaMK II pathway inhibited it. In summary, BMSC osteogenesis on titanium surfaces is suppressed by HG-induced oxidative stress via the ROS/CaMK II/β-catenin signaling axis, which may subsequently impair implant osseointegration.
高糖（HG）诱导的氧化应激通过多种途径影响种植体骨整合。氧化应激被广泛认为会抑制Wnt/β-连环蛋白信号通路，从而损害骨代谢和稳态。然而，关于过量活性氧（ROS）是否通过非经典Wnt/钙调蛋白依赖性蛋白激酶II（CaMK II）途径影响干细胞的成骨分化，鲜有报道。本研究正在探究ROS/CaMK II/β-连环蛋白信号轴影响钛表面骨髓间充质干细胞（BMSC）成骨分化的机制。在本研究中，对钛板进行特殊处理以模拟种植体表面。使用含HG的成骨培养基在钛表面培养BMSC。采用碱性磷酸酶（ALP）活性测定、定量实时PCR（qRT-PCR）和免疫荧光染色等方法，检测HG诱导的过量ROS对BMSC成骨分化以及β-连环蛋白和CaMK II表达的影响。此外，通过分别添加β-连环蛋白和CaMK II的激活剂或抑制剂，观察Wnt/β-连环蛋白和Wnt/CaMK II途径对钛表面BMSC成骨的影响。HG诱导的过量ROS抑制成骨分化。在HG环境中，β-连环蛋白表达降低，而CaMK II表达增加。此外，我们观察到Wnt/β-连环蛋白途径的激活促进成骨，而Wnt/CaMK II途径的激活则抑制成骨。总之，HG诱导的氧化应激通过ROS/CaMK II/β-连环蛋白信号轴抑制钛表面的BMSC成骨，这可能随后损害种植体骨整合。
