Marycz Krzysztof, Kowalczuk Anna, Turlej Eliza, Zachanowicz Emilia, Tomaszewska Anna, Kulpa-Greszta Magdalena, Kępska Martyna, Steczkiewicz Zofia, Pązik Robert
Department of Experimental Biology, Wroclaw University of Environmental and Life Science, Norwida 27, 50-375 Wroclaw, Poland.
National Medicines Institute (NIL), Chelmska 30/34, 00-725 Warszawa, Poland.
Materials (Basel). 2022 Jun 3;15(11):3990. doi: 10.3390/ma15113990.
Osteoporosis is characterized by the reduction of bone mineral density and the weakness of the bone strength leading to fractures. Searching for new compounds that stimulate bone activity and their ability to reconstruct seems to be a promising tool in osteoporosis treatment. Here, we performed analyses comparing the impact of polyrhodanine (PRHD) and its derivatives on the viability (anti-proliferative tests), morphology and mitochondrial network (confocal microscopy) towards pre-osteoblasts (MC3T3-E1 cell line) and osteoclasts (4B12 cell line). Moreover, we assessed the expression of genes associated with the apoptosis, inflammation and osteogenic differentiation by qPCR technique. Our results clearly demonstrated that PRHD and its modification at ratio 10/90 significantly improves the pre-osteoblast's proliferative abilities, while reducing osteoclast function. The observed effects were strongly correlated with the cytoskeleton and mitochondrial network development and arrangement. Additionally, the expression profile of genes revealed enhanced apoptosis of osteoclasts in the case of PRHD and its modification at ratio 10/90. Moreover, in this case we also observed strong anti-inflammatory properties demonstrated by decreased expression of and in pre-osteoblasts and osteoclasts. On the other hand, enhanced expression of the markers associated with bone remodeling, namely, osteopontin (OPN), osteocalcin (OCL) and alkaline phosphatase (ALP), seem to confirm the role of PRHD@MnFeO in the promotion of differentiation of pre-osteoblasts through the axis. Based on these observations, PRHD@MnFeO could be a potential agent in osteoporosis treatment in future, however, further studies are still required.
骨质疏松症的特征是骨矿物质密度降低和骨强度减弱,进而导致骨折。寻找能够刺激骨活性及其重建能力的新化合物似乎是治疗骨质疏松症的一种有前景的方法。在此,我们进行了分析,比较了聚若丹宁(PRHD)及其衍生物对前成骨细胞(MC3T3-E1细胞系)和破骨细胞(4B12细胞系)的活力(抗增殖试验)、形态和线粒体网络(共聚焦显微镜)的影响。此外,我们通过qPCR技术评估了与细胞凋亡、炎症和成骨分化相关基因的表达。我们的结果清楚地表明,PRHD及其10/90比例的修饰显著提高了前成骨细胞的增殖能力,同时降低了破骨细胞的功能。观察到的效果与细胞骨架和线粒体网络的发育及排列密切相关。此外,基因表达谱显示,在PRHD及其10/90比例修饰的情况下,破骨细胞的凋亡增强。此外,在这种情况下我们还观察到了强烈的抗炎特性,表现为前成骨细胞和破骨细胞中 和 的表达降低。另一方面,与骨重塑相关的标志物,即骨桥蛋白(OPN)、骨钙素(OCL)和碱性磷酸酶(ALP)的表达增强,似乎证实了PRHD@MnFeO通过 轴促进前成骨细胞分化的作用。基于这些观察结果,PRHD@MnFeO未来可能成为治疗骨质疏松症的潜在药物,然而,仍需要进一步研究。