gms | German Medical Science

Objectives: Blood supply is of great importance for adequate fracture healing. Delayed union or nonunion of fractures occur more frequently in patients with vascular diseases. A previous study showed that Cxcl9, a chemokine secreted by osteoblasts, negatively regulates angiogenesis and limits blood supply to the intact bone, ultimately resulting in impaired bone formation. Hence, we hypothesize that Cxcl9 not only affects normal bone hemostasis, but also exerts a significant impact on fracture healing.

Methods: Female WT and Cxcl9-deficient (Cxcl9-/-) mice received a femoral osteotomy stabilized by an external fixator (Fx). Femurs were harvested 7, 14 and 21 days post-surgery for micro-CT and histological analyses. Currently, biomechanical testing is performed on fractured femur bones 21d post-surgery. Additionally, the vascularization pattern and expression profiles of specific target genes in the fracture callus will be compared through immunohistochemistry and qRT-PCR, respectively.

Results and Conclusion: Compared to WT mice, Cxcl9-/- mice showed an impaired bone regeneration 14 days and 21 days after fracture in our preliminary results. Micro-CT evaluation revealed a decreased callus volume but increased bone mineralized density (BMD) 21 days after fracture. Histomorphometric quantification showed a reduced percentage of mineralized bone in the total callus area, accompanied by a high rate of incomplete bridging of fracture ends resulting in nonunion. Completed results with biomechanical testing, gene expression analysis, and immunohistochemical analyses of Cd31 and Endomycin-positive vascular structures will be reported at the DKOU 2021. Taking together, our hitherto results suggest that Cxcl9 is crucially involved in the regulation of bone regeneration and may represent a promising therapeutic target to treat patients with impaired bone healing.