Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100050, China.
Beijing Laboratory of Oral Health, Capital Medical University, Beijing, 100069, China.
Stem Cell Res Ther. 2024 Sep 16;15(1):306. doi: 10.1186/s13287-024-03929-4.
Influence on stem cells' angiogenesis and osteogenesis of NAD(P)H Quinone Dehydrogenase 1(NQO1) has been established, but its impact on dental pulp stem cells (DPSCs) is unexplored. An important strategy for the treatment of arteriosclerosis is to inhibit calcium deposition and to promote vascular repair and angiogenesis. This study investigated the function and mechanism of NQO1 on angiogenesis and osteogenesis of DPSCs, so as to provide a new ideal for the treatment of arteriosclerosis.
Co-culture of human DPSCs and human umbilical vein endothelial cells (HUVECs) was used to detect the angiogenesis ability. Alkaline phosphatase (ALP) activity, alizarin red staining (ARS), and transplantation of HA/tricalcium phosphate with DPSCs were used to detect osteogenesis.
NQO1 suppressed in vitro tubule formation, migration, chemotaxis, and in vivo angiogenesis, as evidenced by reduced CD31 expression. It also enhanced ALP activity, ARS, DSPP expression and osteogenesis and boosted mitochondrial function in DPSCs. CoQ10, an electron transport chain activator, counteracted the effects of NQO1 knockdown on these processes. Additionally, NQO1 downregulated MAPK signaling, which was reversed by CoQ10 supplementation in DPSCs-NQO1sh.
NQO1 inhibited angiogenesis and promoted the osteogenesis of DPSCs by suppressing MAPK signaling pathways and enhancing mitochondrial respiration.
烟酰胺腺嘌呤二核苷酸(NAD)(P)H 醌氧化还原酶 1(NQO1)对干细胞的血管生成和成骨作用已得到证实,但对牙髓干细胞(DPSCs)的影响尚未可知。抑制钙沉积和促进血管修复和血管生成是治疗动脉硬化的重要策略。本研究探讨了 NQO1 对 DPSCs 血管生成和成骨作用的功能和机制,以期为动脉硬化的治疗提供新的理想靶点。
采用人牙髓干细胞(DPSCs)与人脐静脉内皮细胞(HUVECs)共培养的方法检测血管生成能力。碱性磷酸酶(ALP)活性、茜素红染色(ARS)和 HA/三钙磷酸盐移植与 DPSCs 检测成骨作用。
NQO1 抑制体外管形成、迁移、趋化性和体内血管生成,表现为 CD31 表达减少。它还增强了 DPSCs 的 ALP 活性、ARS、DSPP 表达和成骨作用,并增强了线粒体功能。电子传递链激活剂 CoQ10 逆转了 NQO1 敲低对这些过程的影响。此外,NQO1 通过抑制 MAPK 信号通路下调 DPSCs-NQO1sh 中的 MAPK 信号通路。
NQO1 通过抑制 MAPK 信号通路和增强线粒体呼吸来抑制血管生成并促进 DPSCs 的成骨作用。