Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Tissue Cell. 2022 Aug;77:101849. doi: 10.1016/j.tice.2022.101849. Epub 2022 Jun 1.
Copper (Cu) ions have been found to exert antibacterial and angiogenic effects. However, some studies have indicated that it inhibits osteogenesis at high concentrations. On the other hand, L-arginine (Arg) is a semi-essential amino acid required for various biological processes, including osteogenic and angiogenic activities. As a result, we hypothesized that combining Arg with Cu ions would reduce its inhibitory effects on osteogenesis while increasing its angiogenic and antibacterial capabilities. To assess osteogenic and angiogenic activities, we employed rat bone marrow mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs), respectively. The gram-positive bacteria Staphylococcus epidermidis (S. epidermidis), Staphylococcus aureus (S. aureus), and the gram-negative bacterium Escherichia coli (E. coli) were used to investigate bacterial behaviors. According to ALP activity and calcium deposition outcomes, copper ions inhibited osteogenic development of MSCs at 100 µM; however, Arg supplementation somewhat mitigated the inhibitory effects. Furthermore, Copper and Arg synergistically stimulated migration and tube formation of HUVECs. According to our findings, copper ions and Arg in the range of 1-100 µM had no antibacterial effect on any examined bacteria. However, at a dose of 20 mM, copper demonstrated antibacterial activity, which was boosted by Arg. Overall, these findings suggest that a combination of copper and Arg may be more beneficial for bone regeneration than either copper or Arg alone.
铜 (Cu) 离子已被发现具有抗菌和促血管生成作用。然而，一些研究表明，高浓度的铜离子会抑制成骨作用。另一方面，L-精氨酸 (Arg) 是一种半必需氨基酸，参与多种生物过程，包括成骨和血管生成活动。因此，我们假设将 Arg 与 Cu 离子结合使用可以降低其对成骨作用的抑制作用，同时提高其促血管生成和抗菌能力。为了评估成骨和血管生成活性，我们分别使用大鼠骨髓间充质干细胞 (MSCs) 和人脐静脉内皮细胞 (HUVECs)。选用革兰氏阳性菌表皮葡萄球菌 (S. epidermidis)、金黄色葡萄球菌 (S. aureus) 和革兰氏阴性菌大肠杆菌 (E. coli) 来研究细菌行为。根据碱性磷酸酶 (ALP) 活性和钙沉积结果，100μM 的铜离子抑制了 MSCs 的成骨发育；然而，Arg 的补充在一定程度上减轻了这种抑制作用。此外，铜和 Arg 协同刺激了 HUVECs 的迁移和管腔形成。根据我们的发现，1-100μM 范围内的铜离子和 Arg 对任何检测到的细菌都没有抗菌作用。然而，在 20mM 的剂量下，铜表现出抗菌活性，Arg 增强了这种活性。总的来说，这些发现表明，铜和 Arg 的组合可能比单独使用铜或 Arg 更有利于骨再生。
