PDF(Pubmed)
Abstract：
Osteoporosis is the most common metabolic bone disorder and is characterized by decreased bone density, which has a relationship with the quality of life among the aging population. Previous research has found that activation of the dopamine D1 receptor can improve bone mass formation. SKF38393 is an agonist of dopamine D1 receptors. However, as a small-molecule drug, SKF38393 is unstable and releases quickly. The aim of this study was to prototype polylactic-co-glycolic acid (PLGA)/SKF38393 microspheres and assess their potential osteogenic effects compared to those under the free administration of SKF38393. The cytocompatibility of PLGA/SKF38393 was determined via CCK-8 and live/dead cell staining; the osteogenic effects in vitro were determined with ALP and alizarin red staining, qRT-PCR, and Western blotting; and the in vivo effects were assessed using 25 Balb/c mice. We also used a PCR array to explore the possible signaling pathway changes after employing PLGA/SKF38393. Our experiments demonstrated that the osteogenic effect of D1Rs activated by the PLGA/SKF38393 microsphere was better than that under free administration, both in vitro and in vivo. According to the PCR array, this result might be associated with six signaling pathways (graphical abstract). Ultimately, in this study, we prototyped PLGA/SKF38393, demonstrated its effectiveness, and preliminarily analyzed its mechanism of action.
摘要：
骨质疏松症是最常见的代谢性骨疾病，其特征是骨密度降低，这与老龄人口的生活质量有关。先前的研究发现，多巴胺D1受体的激活可以改善骨量的形成。SKF38393是多巴胺D1受体的激动剂。然而,作为一种小分子药物，SKF38393不稳定，释放迅速。这项研究的目的是建立聚乳酸-羟基乙酸共聚物（PLGA）/SKF38393微球的原型，并评估其与自由施用SKF38393相比的潜在成骨作用。通过CCK-8和活/死细胞染色确定PLGA/SKF38393的细胞相容性；用ALP和茜素红染色确定体外成骨作用，qRT-PCR,和Western印迹;并且使用25只Balb/c小鼠评估体内效果。我们还使用PCR阵列来探索使用PLGA/SKF38393后可能的信号通路变化。我们的实验表明，PLGA/SKF38393微球激活的D1R的成骨作用优于自由给药，在体外和体内。根据PCR阵列,这一结果可能与6条信号通路有关(图形摘要).最终,在这项研究中，我们制作了PLGA/SKF38393原型，证明了它的有效性，并初步分析了其作用机制。
