Department of Orthopedic Surgery, The 1st Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.
Department of Orthopedic Surgery, People's Hospital of Qinghai Province, Xining, Qinghai, People's Republic of China.
Int J Nanomedicine. 2020 Sep 29;15:7143-7153. doi: 10.2147/IJN.S245870. eCollection 2020.
Tobacco mosaic virus-based nanoparticles (TMV VNPs) were previously shown to promote osteogenic differentiation in vitro. This study aims to investigate whether and how TMV VNPs impact on osteoclastogenesis in vitro and bone injury healing in vivo.
Raw264.7 cells were cultured in osteoclastogenic medium in culture plates coated with or without TMV and TMV-RGD1 VNPs, followed by TRAP staining, RT-qPCR and WB assessing expression of osteoclastogenic marker genes, and immunofluorescence assessing NF-κB activation. TMV and TMV-RGD1-modified hyaluronic acid hydrogel were used to treat mouse tibial bone injury. Bone injury healing was checked by micro-CT and Masson staining.
TMV and TMV-RGD1 VNPs significantly inhibited osteoclast differentiation and downregulated the expression of osteoclastogenic marker genes Ctr, Ctsk, Mmp-9, Rank, and Trap. Moreover, TMV and TMV-RGD1 VNPs inhibited NF-κB p65 phosphorylation and nuclear translocation, as well as activation of mTOR/AKT signaling pathway. TMV and TMV-RGD1-modified HA hydrogel strongly promoted mouse tibial bone injury with increased bone mass compared to plain HA hydrogel. The amount of osteoclasts was significantly reduced in TMV and TMV-RGD1 treated mice. TMV-RGD1 was more effective than TMV in inhibiting osteoclast differentiation and promoting bone injury repair.
These data demonstrated the great potential of TMV VNPs to be developed into biomaterial for bone injury repair or replacement.
先前的研究表明，基于烟草花叶病毒的纳米颗粒（TMV VNPs）可促进体外成骨分化。本研究旨在探讨 TMV VNPs 是否以及如何影响体外破骨细胞分化和体内骨损伤愈合。
Raw264.7 细胞在涂有或未涂 TMV 和 TMV-RGD1 VNPs 的培养板中于成骨细胞分化培养基中培养，随后通过 TRAP 染色、RT-qPCR 和 WB 评估破骨细胞分化标志物基因的表达，以及免疫荧光评估 NF-κB 激活情况。使用 TMV 和 TMV-RGD1 修饰的透明质酸水凝胶治疗小鼠胫骨骨损伤。通过 micro-CT 和 Masson 染色检查骨损伤愈合情况。
TMV 和 TMV-RGD1 VNPs 显著抑制破骨细胞分化，并下调破骨细胞分化标志物基因 Ctr、Ctsk、Mmp-9、Rank 和 Trap 的表达。此外，TMV 和 TMV-RGD1 VNPs 抑制 NF-κB p65 磷酸化和核转位，以及 mTOR/AKT 信号通路的激活。与普通透明质酸水凝胶相比，TMV 和 TMV-RGD1 修饰的透明质酸水凝胶强烈促进小鼠胫骨骨损伤，增加骨量。TMV 和 TMV-RGD1 处理组小鼠的破骨细胞数量明显减少。TMV-RGD1 在抑制破骨细胞分化和促进骨损伤修复方面比 TMV 更有效。
这些数据表明，TMV VNPs 具有巨大的潜力，可开发为用于骨损伤修复或替代的生物材料。
