Abstract:Objective To investigate the influences of Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation on protein kinase signaling pathway in bone and joint tumor of rats. Methods Rat bone and joint tumor models were established by injecting osteosarcoma cells into bone marrow cavity in 24 healthy male SD rats (control group) and 24 KRAS- mutant male SD rats (mutation group).The expression of Toll like receptor 4 (TLR4) signaling pathway, the expressions of mRNA and protein of protein kinase B (Akt) in synovial tissue and the serum levels of IL-6 and TNF-α were detected at 4 and 8 weeks after modeling. Results The serum IL-6 and TNF-α levels in mutation group were significantly higher than those in control group at 4 and 8 weeks after model establishment (all P<0.01).In control group, the endothelial cells of the knee joint were intact, mainly composed of smooth muscle cells and elastic fibers, and the internal force plate were continuously regularized without proliferation and lipid deposition.However, in mutation group, thickening of intima, partial occlusion of lumen, a large number of vacuolar cells and lipid deposition presented in the knee joint.The relative expression levels of TLR4 and Akt mRNA and protein in synovial tissue in mutation group were significantly higher than those in control group (P<0.05, P<0.01). Conclusion KRAS mutation may activate the expressions of TLR4 and Akt of protein kinase signaling pathway , thus promoting the release of inflammatory factors and aggravating the condition of bone and joint tumors in rats.