Lactoferrin Is a Potential Activator of the Vitamin D Receptor in Its Regulation of Osteogenic Activities in C57BL/6J Mice and MC3T3-E1 Cells
Lactoferrin Is a Potential Activator of the Vitamin D Receptor in Its Regulation of Osteogenic Activities in C57BL/6J Mice and MC3T3-E1 Cells
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乳铁蛋白是维生素 D 受体的潜在激活剂，可调节 C57BL/6J 小鼠和 MC3T3-E1 细胞的成骨活性
DOI：
10.1093/jn/nxab105
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发表时间：
2021-05-13
影响因子：
4.2
通讯作者：
Guo, Huiyuan
中科院分区：
文献类型：
--
作者：
Li, Yixuan;Huang, Jiaqiang;Guo, Huiyuan
背景：乳铁蛋白（LF）具有促进骨愈合的作用，维生素D受体（VDR）介导维生素D对骨的作用。我们假设LF通过增加VDR表达来改善骨健康。目的：我们试图确定VDR激活在LF诱导的体内和体外成骨活性中的作用以及潜在的分子机制。（4周龄）随机分为6组，（VDD; 0 IU/kg）或维生素D正常饮食（VDN; 1000 IU胆钙化物/kg），并通过管饲给予安慰剂或LF（100或1000 mg/kg体重），持续24周。使用显微CT分析松质骨结构，并通过免疫组织化学评估VDR表达。在体外，用100 μ g LF/mL处理MC 3 T3-E1细胞以评价其对VDR表达的影响。最后，通过染色质免疫沉淀试验证实LF直接募集到Vdr启动子。结果：LF 100和1000 mg/kg组小鼠骨密度较对照组增加6.5%（P < 0.05），骨中VDR表达增强。在VDN饮食的小鼠骨骼中也观察到VDR表达增加，但在VDD饮食中效果更明显。在体外实验中，LE作用后2 h，Vdr mRNA表达量增加18倍（P < 0.05）。结论：LF作为VDR的潜在激活剂，在体内外均能促进成骨细胞的生长，并能促进成骨细胞的增殖。这表明富含LF的乳制品可以作为改善骨骼健康的功能性食品。
Background: Lactoferrin (LF) has been shown to promote bone anabolism, and the vitamin D receptor (VDR) mediates the effects of vitamin D on bone. We hypothesized that LF improves bone health by increasing VDR expression.Objectives: We sought to determine the role of VDR activation in LF-induced osteogenic activity in vivo and in vitro and the underlying molecular mechanisms.Methods: Sixty male C57BL/6J mice (aged 4 wk) were randomly assigned into 6 groups and fed vitamin D-deficient (VDD; 0 IU/kg) or vitamin D-normal diet (VDN; 1000 IU cholecalciferoVkg) and administered placebo or LF (100 or 1000 mg/kg body weight) by gavage for 24 wk. Trabecular bone structure was analyzed using micro-CT, and VDR expression was assessed by immunohistochemistry. In vitro, MC3T3-E1 cells were treated with 100 mu g LF/mL to evaluate its effect on VDR expression. Finally, the direct recruitment of LF to the Vdr promoter was confirmed by chromatin immunoprecipitation assay. In addition, cells were transfected with pGL3-basic Vdr vector for monitoring Vdr promoter activation using luciferase assays.Results: LF supplementation at 100 and 1000 mg/kg revealed an similar to 6.5% (P < 0.05) increase in bone mineral density in mice on VDD diet and exhibited an enhanced expression of VDR in bone compared with control. This increased expression of VDR was also observed in the bone of mice on the VDN diet, but the effect was more pronounced in VDD diet. In vitro, compared with the control group, Vdr mRNA expression was 18 times greater (P < 0.05) and peaked at 2 h posttreatment of LE. By cotransfection of the pGL3-basic Vdr vector, LF induced luciferase activity by 30% (P < 0.05) in MC3T3-E1 cells.Conclusions: In vivo and in vitro, LF, a potential activator of VDR, promotes osteogenesis. This suggests that dairy products, which are rich in LF, may serve as a functional food to improve bone health.