Abstract
Vancomycin is an effective antibiotic for treatment of bone infection caused by Staphylococcus aureus, however, a high local concentration of vancomycin might induce a delay in bone union. Icariin has been reported to suppress osteoclastogenes and promote osteogenesis. Our study aimed to investigate the effect of icariin on bone repair after anti-infection treatment in vivo and to explore the resisting effect of icariin on rat calvarial osteoblasts (ROBs) inhibited with high doses of vancomycin. Rabbits with bone infection of S. aureus were treated with implanted vancomycin-calcium sulfate (VCS) and icariin at 10.86 mg/kg/day for consecutive 8 weeks. Micro-CT, morphology, blood biochemistry were evaluated. In addition, ROBs were treated with vancomycin and icariin at different doses. Cell proliferation and differentiation capabilities, BMP2, Runx2, OPG, RANKL mRNA levels and protein expression were assessed. The results indicated that high dose of vancomycin significantly decreased bone mass and inhibited osteocalcin secretion; icariin increased these indicators compared with the single vancomycin treatment. Over 0.1 mg/mL of vancomycin inhibited the proliferation and differentiation of ROBs, while icariin resisted the inhibition of vancomycin by regulating cell cycle and promoting the Alkaline phosphatase (ALP) activity. Moreover, icariin promote bone formation by up-regulating BMP2/Runx2 and OPG/RANKL pathways. Icariin exhibited osteoplastic properties on osteoblasts that had been inhibited with high doses of vancomycin. Therefore, icariin is helpful for post-infection treatment of bone infection.
Highlights
MATERIALS AND METHODSMany factors contribute to the increase in severe bone infections and tissue suppurations, including accidents and the increased use of orthopedic devices
vancomycin-calcium sulfate (VCS)-H and low dose VCS (VCS-L) treatment significantly decreased the levels of white blood count (WBC) from 18.21 × 109/L to less than 10 × 109/L, and decreased the levels of high sensitive C-reactive protein (CRP) from 9.54 to 4 mg/L at the 4th week after treatment
There was no significant difference in CRP or WBC in the control group, high dose VCS (VCS-H), VCS-L, and VCS-icariin groups after treatment, which illustrated that VCS had an excellent antiinflammatory effect
Summary
MATERIALS AND METHODSMany factors contribute to the increase in severe bone infections and tissue suppurations, including accidents and the increased use of orthopedic devices. Bone infection has various impacts on patients, such as delayed unions and amputation (Hassani Besheli et al, 2017). In 10–15% of cases of bone infection, patients experienced a long bone union process, delayed union or non-union after anti-infection treatment. The factors that lead to delayed union are still unknown; some reports stated that it resulted from inflammation or even a high concentration of antibiotic medication (Eder et al, 2016; Mendoza et al, 2016). The main role of the local placement of VCS is to release vancomycin in the infected marrow cavity and bone to inhibit bacterium and avoid potential infection. A high dose of VCS (more than 1 g of vancomycin) was usually implanted into the local site to control the repeated infection in some cases. A previous study indicated that a high concentration of vancomycin (more than 4 mg/mL) can decrease the number of osteogenic cells, induce a loss in pseudopodia formation and alter the normal shape of the cytoplasm (Rathbone et al, 2011; Goldschmidt et al, 2016)
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