Lactoferrin is a potent regulator of bone cell activity and increases bone. formation in vivo
Lactoferrin is a potent regulator of bone cell activity and increases bone. formation in vivo
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DOI：
10.1210/en.2003-1307
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发表时间：
2004-09-01
期刊：
影响因子：
4.8
通讯作者：
Reid, IR
中科院分区：
文献类型：
--
作者：
Cornish, J;Callon, KE;Reid, IR
乳铁蛋白是一种结合铁的糖蛋白，存在于上皮分泌物，如牛奶和中性粒细胞的次级颗粒中。我们发现它存在于刺激成骨细胞生长的牛奶蛋白中，所以我们评估了它对骨细胞功能的影响。在人或大鼠成骨样细胞的原代或细胞系培养中，乳铁蛋白在生理浓度（1-100马克杯/毫升）下产生了胸苷掺入的大量剂量相关增加。最大刺激是对照组的5倍。乳铁蛋白还能促进成骨细胞分化，减少成骨细胞凋亡，可达50-70%。同样，乳铁蛋白刺激原代软骨细胞增殖。纯化的、重组的、人的或牛的乳铁蛋白具有相似的效力。在小鼠骨髓培养中，破骨细胞的生成呈剂量依赖性地减少，100杯/毫升的乳铁蛋白完全阻止了破骨细胞的生成，与核因子- κ b配体受体激活剂的表达减少有关。相比之下，乳铁蛋白对分离的成熟破骨细胞的骨吸收没有影响。在成年小鼠颅骨上给予乳铁蛋白5天。用荧光标记评估，新骨形成在4毫克剂量的乳铁蛋白的作用下增加了4倍。因此，乳铁蛋白对成骨细胞具有强大的合成代谢、分化和抗凋亡作用，并抑制破骨细胞的发生。乳铁蛋白是骨质疏松等骨疾病的潜在治疗靶点，可能是骨生长的重要生理调节剂。
Lactoferrin is an iron-binding glycoprotein present in epithelial secretions, such as milk, and in the secondary granules of neutrophils. We found it to be present in fractions of milk protein that stimulated osteoblast growth, so we assessed its effects on bone cell function. Lactoferrin produced large, dose-related increases in thymidine incorporation in primary or cell line cultures of human or rat osteoblast-like cells, at physiological concentrations (1-100 mug/ml). Maximal stimulation was 5-fold above control. Lactoferrin also increased osteoblast differentiation and reduced osteoblast apoptosis by up to 50-70%. Similarly, lactoferrin stimulated proliferation of primary chondrocytes. Purified, recombinant, human, or bovine lactoferrins had similar potencies. In mouse bone marrow cultures, osteoclastogenesis was dose-dependently decreased and was completely arrested by lactoferrin, 100 mug/ml, associated with decreased expression of receptor activator of nuclear factor-kappaB ligand. In contrast, lactoferrin had no effect on bone resorption by isolated mature osteoclasts. Lactoferrin was administered over calvariae of adult mice for 5 d. New bone formation, assessed using fluorochrome labels, was increased 4-fold by a 4-mg dose of lactoferrin. Thus, lactoferrin has powerful anabolic, differentiating, and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis. Lactoferrin is a potential therapeutic target in bone disorders such as osteoporosis and is possibly an important physiological regulator of bone growth.