Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
Bioorg Med Chem Lett. 2020 Jun 1;30(11):127137. doi: 10.1016/j.bmcl.2020.127137. Epub 2020 Mar 24.
In recent years, phytochemicals have been widely researched and utilized for the treatment of various medical conditions such as cancer, cardiovascular diseases, age-related problems and are also said to have bone regenerative effects. In this study, phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol), an acyclic unsaturated diterpene alcohol and a secondary metabolite derived from aromatic plants was investigated for its effect on osteogenesis. Phytol was found to be nontoxic in mouse mesenchymal stem cells (C3H10T1/2). At the cellular level, phytol-treatment promoted osteoblast differentiation, as seen by the increased calcium deposits. At the molecular level, phytol-treatment stimulated the expression of Runx2 (a bone-related transcription factor) and other osteogenic marker genes. MicroRNAs (miRNAs) play an essential role in controlling bone metabolism by targeting genes at the post-transcriptional level. Upon phytol-treatment in C3H10T1/2 cells, mir-21a and Smad7 levels were increased and decreased, respectively. It was previously reported that mir-21a targets Smad7 (an antagonist of TGF-beta1 signaling) and thus, protects Runx2 from its degradation. Thus, based on our results, we suggest that phytol-treatment promoted osteoblast differentiation in C3H10T1/2 cells via Runx2 due to downregulation of Smad7 by mir-21a. Henceforth, phytol was identified to bolster osteoblast differentiation, which in turn may be used for bone regeneration.
近年来,植物化学物质已被广泛研究和应用于治疗各种医学病症,如癌症、心血管疾病、与年龄相关的问题,并且据说还具有骨再生作用。在这项研究中,植醇(3,7,11,15-四甲基十六-2-烯-1-醇),一种环状不饱和二萜醇和衍生自芳香植物的次级代谢产物,被研究用于其对成骨的作用。植醇在小鼠间充质干细胞(C3H10T1/2)中被发现是无毒的。在细胞水平上,植醇处理促进成骨细胞分化,如增加钙沉积所表明的。在分子水平上,植醇处理刺激 Runx2(与骨相关的转录因子)和其他成骨标记基因的表达。微小 RNA(miRNA)通过在转录后水平靶向基因在控制骨代谢中发挥着重要作用。在 C3H10T1/2 细胞中用植醇处理后,mir-21a 和 Smad7 的水平分别增加和减少。先前有报道称,mir-21a 靶向 Smad7(TGF-β1 信号的拮抗剂),从而保护 Runx2 免受其降解。因此,根据我们的结果,我们建议植醇处理通过 Runx2 促进 C3H10T1/2 细胞中的成骨细胞分化,因为 mir-21a 下调 Smad7。因此,植醇被鉴定为促进成骨细胞分化,这反过来又可用于骨再生。