Discussion
These data demonstrated the great potential of TMV VNPs to be developed into biomaterial for bone injury repair or replacement.
Methods
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.
Results
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.