Li Pan, Wang Jing, Wang Huan, Liu Songchun, Zhang Qibin
Department of Orthopaedics, Lequn Branch, The First Hospital of Jilin University, Changchun, Jilin, 130000, China.
Department of Orthopedics, Ezhou Central Hospital, Ezhou, Hubei, 436000, China.
Open Life Sci. 2025 Jun 17;20(1):20221032. doi: 10.1515/biol-2022-1032. eCollection 2025.
This investigation explores the impact of hesperidin and its zinc(ii) complex on osteoblast differentiation and subsequent bone formation. The biocompatibility of synthesized complexes (0-20 μg/mL) was assessed using mouse mesenchymal stem cells, while toxicity was evaluated using a chick embryo model. Both hesperidin and its zinc(ii) complex were found to be non-toxic at a concentration of 10 μg/mL. Notably, these compounds significantly increased alkaline phosphatase activity and enhanced calcium deposition. Molecular analyses revealed upregulation of Runx2 and type 1 collagen mRNA expression, along with increased levels of osteonectin and osteocalcin proteins, while negative regulators of osteoblast differentiation (Smad7, Smurf1, HDAC7) were downregulated. A new aspect of this study is demonstrating that the zinc(ii) complex of hesperidin uniquely enhances osteogenic activity compared to hesperidin alone, highlighting its potential to improve bone formation significantly. Additionally, we elucidated the role of miR-143-3p in mediating these effects, achieved through HDAC7 suppression and enhanced Runx2 expression, assessed using the pmirGLO dual luciferase reporter system. Zebrafish studies further demonstrated the complexes' effects on bone formation, revealing increased osteoblastic activity and improved calcium-to-phosphorus ratios in regenerated scales. These findings underscore the potential of hesperidin-Zn(ii) as a promising therapeutic agent for bone tissue engineering.
本研究探讨橙皮苷及其锌（II）配合物对成骨细胞分化及后续骨形成的影响。使用小鼠间充质干细胞评估合成配合物（0 - 20μg/mL）的生物相容性，同时使用鸡胚模型评估其毒性。发现橙皮苷及其锌（II）配合物在浓度为10μg/mL时均无毒。值得注意的是，这些化合物显著提高了碱性磷酸酶活性并增强了钙沉积。分子分析显示Runx2和I型胶原蛋白mRNA表达上调，骨连接蛋白和骨钙素蛋白水平增加，而成骨细胞分化的负调节因子（Smad7、Smurf1、HDAC7）下调。本研究的一个新方面是表明，与单独的橙皮苷相比，橙皮苷的锌（II）配合物独特地增强了成骨活性，突出了其显著改善骨形成的潜力。此外，我们阐明了miR - 143 - 3p在介导这些效应中的作用，这是通过使用pmirGLO双荧光素酶报告系统评估的HDAC7抑制和Runx2表达增强实现的。斑马鱼研究进一步证明了这些配合物对骨形成的影响，揭示了再生鳞片中成骨细胞活性增加和钙磷比改善。这些发现强调了橙皮苷 - 锌（II）作为骨组织工程有前景的治疗剂的潜力。
