Teng Minhua, Yuan Xiao, Wang Dashan, Gao Hui, Zhang Kaiyue, Wang Wenxue, Zhao Baodong
Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
School of Stomatology, Qingdao University, Qingdao 266003, China.
Stem Cells Int. 2022 Aug 16;2022:1395299. doi: 10.1155/2022/1395299. eCollection 2022.
Scutellarin is known as a safe, effective, and low-cost traditional Chinese medicine and has a variety of biological activities. Studies reported that the scutellarin loaded on ultradeformable nanoliposome scutellarin EDTMP (S-UNL-E) could promote osteoblast differentiation and bone formation in vitro. However, its effect on promoting osteogenesis in vivo is still unclear. In this study, pharmacology network and transcriptome sequencing were used to screen the potential targets and pathways of scutellarin in treating osteoporosis. The female Sprague-Dawley (SD) rats were operated on with bilateral oophorectomy and femoral defect to establish an osteoporosis model and then treated separately with bone dust, single scutellarin, 40 mg/kg ultradeformable nanoliposome scutellarin (S-UNL), and the optimal concentration of 40 mg/kg S-UNL-E for a total of 56 d to detect the parameters of trabecular bones. And qRT-PCR and western blot were performed to determine the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), alkaline phosphatase (ALP), transcription factor 4 (TCF4), and -catenin. Results of microscopic computed tomography (Micro-CT) of trabecular bones showed that single scutellarin, S-UNL, and S-UNL-E all promoted the bone formation of osteoporotic rats, in which S-UNL-E manifested the most remarkable therapeutic effect. And it is found that 40 mg/kg of S-UNL-E increased the expression of PTGS2, ALP, TCF4, and -catenin, which indicated that S-UNL-E stimulated the secretion of ALP in bone defect areas to promote bone healing, and increased PTGS2 expression thereby enhancing the transcription and translation of key gene -catenin and TCF4 in the Wnt/-catenin signaling pathway to treat osteoporotic rats.
灯盏花素是一种安全、有效且低成本的传统中药，具有多种生物活性。研究报道，负载于超变形纳米脂质体的灯盏花素乙二胺四甲基膦酸（S-UNL-E）在体外可促进成骨细胞分化和骨形成。然而，其在体内促进成骨的作用仍不清楚。本研究采用药理学网络和转录组测序来筛选灯盏花素治疗骨质疏松症的潜在靶点和途径。对雌性Sprague-Dawley（SD）大鼠进行双侧卵巢切除和股骨缺损手术以建立骨质疏松模型，然后分别用骨粉、单一灯盏花素、40mg/kg超变形纳米脂质体灯盏花素（S-UNL）以及40mg/kg S-UNL-E的最佳浓度进行治疗，共56天，以检测小梁骨参数。并进行qRT-PCR和蛋白质免疫印迹法以确定前列腺素内过氧化物合酶2（PTGS2）、碱性磷酸酶（ALP）、转录因子4（TCF4）和β-连环蛋白的表达。小梁骨的显微计算机断层扫描（Micro-CT）结果显示，单一灯盏花素、S-UNL和S-UNL-E均促进了骨质疏松大鼠的骨形成，其中S-UNL-E表现出最显著的治疗效果。并且发现40mg/kg的S-UNL-E增加了PTGS2、ALP、TCF4和β-连环蛋白的表达，这表明S-UNL-E刺激骨缺损区域ALP的分泌以促进骨愈合，并增加PTGS2表达，从而增强Wnt/β-连环蛋白信号通路中关键基因β-连环蛋白和TCF4的转录和翻译，以治疗骨质疏松大鼠。
