| Objective: This study was to evaluate the effect of lactoferrin(LF) on bone mass and the expression of insulin-like growth factor I(IGF-I), insulin-like growth factor binding protein-3(IGFBP-3), insulin-like growth factor binding protein-5(IGFBP-5) in femur and to explore the therapeutic effect and the molecular mechanism that mediate the anabolic action of LF in osteoporosis.Methods: Six-month-old female Sprague-Dawley rats(n=70) were randomly divided into the following groups: ovariectomy untreated group(Con); sham-operated group(Sham); ovariectomy 17β-estradiol(0.1mg/kg·wk) treated group(E2); ovariectomy BSA(0.1g/kg·d) treated group(BSA); ovariectomy LF(0.1g/kg·d) treated group(LF1); ovariectomy LF(1g/kg·d) treated group(LF2); and ovariectomy LF(2g/kg·d) treated group(LF3). After 24 weeks of treatment, the bone mass of metaphysis under the epiphyseal of left tibia were made to be HE staining biopsy and and then scanned by optical microscope, the ratio between the mean trabecular area and marrow cavity were analyzed by Image-Pro Plus 6.0, and the levels of IGF-I, IGFBP-3, IGFBP-5 m RNA in the right femur were measured by quantitative real-time reverse transcription PCR(q RT-PCR).Results: 1. The body weights of all the rats were not significantly different before the treatment(all P>0.05). By the end of the 24-week experiment, all of the rats had increased their body weights. The rats in Con group tended to gain more weight than those in Sham and E2 group(all P<0.05). The final body weights in BSA-treated and LF-treated rats tended to be lower than those of the Con group; however, these differences were not statistically significant(all P>0.05).2. After treated for 6 months, trabecular density in the Sham and the E2 group was more compact than in the Con and the BSA group. The trabecular density in the LF1-3 group was more compact than in the Con and the BSA group, but not as significant as the Sham and the E2 group, and it was difficult to identify the trabecular density among each group of LF1-3 under the optical microscope. The Image-Pro Plus 6.0 showed that the ratio between the trabecular area and marrow cavity in Sham and the E2 group were significantly higher than the Con, the BSA group and each group of LF1-3(all P<0.01). The differences between Sham and the E2 group, Con and the BSA group, and each group of LF1-3 were not statistically significant(all P>0.05).3. After treated for 6 months,the Sham group, the E2 group and the LF1-3 group(all P<0.01) caused a significant increase in the IGF- I m RNA levels as compared with the Con group. The Con group caused a significant decrease in the IGFBP-3 m RNA levels as compared with the Sham group and the E2 group(P<0.01), but it caused a significant increase in the LF1-3group(all P<0.01). In addition, the Sham group, the E2 group(all P<0.01) and the LF2-3 group(P<0.05 and P<0.01) caused a significant increase in the IGFBP-5 m RNA levels as compared with the Con group.Conclusions: 1. The replication animal model of osteoporosis was successful. 2. Lactoferrin have potential therapeutic effect on osteoporosis which can increase bone density in ovariectomized rats and be prevent from bone loss after ovariectomy. 3. The increased bone mass and reduced bone loss of the ovariectomized rats that treated with Lactoferrin may have occurred via the boost of IGF-I, IGFBP-3 and IGFBP-5. |
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