Abstract
Introduction
The therapeutic potential of hematopoietic stem cells for fracture healing has been demonstrated with mechanistic insight of vasculogenesis and osteogenesis enhancement. Lnk has recently been proved an essential inhibitory signaling molecule in SCF-c-Kit signaling pathway for stem cell self-renewal demonstrating enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice. We investigated the hypothesis that down regulation of Lnk enhances regenerative response via vasculogenesis and osteogenesis in fracture healing.
Methods
A reproducible model of femoral fracture was created in mice. Immediately after fracture creation, mice received local administration of the following materials with AteloGene, 10μM (1)Lnk siRNA, (2)control siRNA.
Results
Lnk group demonstrated more prompt fracture repair than control group. The functional bone healing was also significantly greater in Lnk group. Immunohistochemical staining and the mRNA expressions in fracture sites indicated the superior ability for angiogenesis and osteogenesis in Lnk group. Moreover, Lnk siRNA transfected cells showed high capacity of colony formation in vitro.
Conclusion
We clarified that negatively controlled Lnk system contributed to a favorable environment for fracture healing by enhancing vasculogenesis and osteogenesis. These findings suggest that down regulation of Lnk may have a clinical potential for faster fracture healing, which contributes to reduce delayed union or nonunion.