Effect Of Lactoferrin On Bone Metabolism In SAMP6 Mice And Its Relationship With IGF-1

Object: After feeding lactoferrin in senile osteoporosis model mice,the effects of lactoferrin on bone microarchitecture and bone metabolism balance in SAMP6 mice were observed.The relationship between lactoferrin and senile osteoporosis and IGF-1 signaling pathway was also discussed.Methods: Five months old SAMP6 mice were randomly divided into normal saline group and lactoferrin intervention group,and SAMR1 mice of the same age were used as normal controls,with 15 mice in each group.According to previous studies,the daily dose of lactoferrin administered is 2 g/kg*d.Two months later,the femur of the mouse was examined by HE staining and Micro-CT tomography to observe the improvement of bone morphology and bone microstructure of SAMP6 mice by lactoferrin.The bone microstructural parameters related to bone density,trabecular volume ratio,number of trabecular bone,thickness and resolution were obtained.To observe the effects of lactoferrin on bone metabolism in SAMP6 mice,serum calcium,phosphorus and alkaline phosphatase assays and Real time-PCR were used to detect bone formation and bone resorption factors.Real time-PCR was used to detect the expression level of Igf-1,and the related pathway protein p-Akt immunohistochemical staining was used to detect the relationship between lactoferrin and IGF-1 signaling pathway.Results: After 2 months of feeding lactoferrin,the bone morphology and bone microstructure of SAMP6 mice were improved compared with SAMP6 mice fed saline.The BMD,BV/TV and Tb.Th of bone microstructural parameters were significantly higher than those of SAMP6 mice,and the Tb.Sp was significantly lower(P<0.05),but the improvement of Tb.N was not obvious.Serum calcium,phosphorus and alkaline phosphatase reflect the level of bone metabolism in the whole body.Their content is significantly improved compared with the SAMP6 group.The calcium and alkaline phosphatase levels are significantly increased,and the serum phosphorus content is decreased.The difference is statistically significant(P<0.05).In addition,serum lactoferrin concentration in SAMP6 mice was significantly lower than that in SAMR1 mice.Serum lactoferrin and iron levels were significantly increased after lactoferrin feeding,and the difference was statistically significant(P<0.05).Lactoferrin can up-regulate the expression of bone formation factors(Bglap,Bmp2,Opg)in bone,and the expression level of bone resorption factor(Rankl)is down-regulated(P<0.05).After feeding lactoferrin,the expression level of IGF-1 and related pathway protein p-Akt was significantly increased.The results were also significantly different by quantitative and semi-quantitative(P<0.05).Conclusion: 1.Lactoferrin can improve the bone microstructure of SAMP6 mice,increase bone mass,and balance bone metabolism.2.Lactoferrin may affect the bone metabolism and bone microstructure of senile osteoporosis through the IGF-1 related signaling pathway.