利用基因敲除小鼠模型评价牛源骨桥蛋白的生物活性。
Evaluation of Bioactivities of Bovine Milk Osteopontin Using a Knockout Mouse Model.
机构信息
Department of Nutrition, University of California, Davis, CA.
出版信息
J Pediatr Gastroenterol Nutr. 2020 Jul;71(1):125-131. doi: 10.1097/MPG.0000000000002702.
OBJECTIVES
Osteopontin (OPN) is a multifunctional protein present abundantly in human milk, but at low levels in bovine milk and infant formula. Bovine milk OPN (bmOPN) is commercially available, and may therefore, be added to formula. OPN exerts its multiple functions by binding to its receptors to activate cell signaling pathways. The OPN receptor (integrin)-binding site is conserved across species; therefore, bmOPN may exert bioactivities in humans and mice. The objective of the present study was to evaluate bioactivities of bmOPN using an established OPN knock-out (KO) mouse model.
METHODS
We evaluated bioactivities of bmOPN, including effects on intestinal growth, immune response, and brain development. In the present study, wild-type (WT) pups were nursed by WT dams, KO dams, or KO dams with bmOPN supplementation from postnatal days 1 to 21 (P1--P21).
RESULTS
Our results show that orally ingested bmOPN is partly resistant to in vivo gastrointestinal digestion, and supplemental bmOPN exhibited similar effects as mouse milk OPN (mmOPN) on promoting growth of the small intestine revealed by histological analysis of duodenum villus height and crypt depth at P10, on modifying TNF-α response against a LPS challenge at P30, as well as promoting brain myelination by increasing expression of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) and improving cognitive development.
CONCLUSIONS
Our finding that bmOPN with an amino acid sequence different from mmOPN but with a conserved integrin binding site exerts bioactivities similar to mmOPN suggests that bmOPN may provide bioactivities to human infants when added to formula.
目的
骨桥蛋白（OPN）是一种多功能蛋白，在人乳中含量丰富，但在牛乳和婴儿配方奶粉中含量较低。牛乳 OPN（bmOPN）可商业化获取，因此可能会被添加到配方奶粉中。OPN 通过与受体结合发挥其多种功能，从而激活细胞信号通路。OPN 受体（整合素）结合位点在物种间是保守的；因此，bmOPN 可能在人和小鼠中发挥生物活性。本研究的目的是使用已建立的 OPN 敲除（KO）小鼠模型来评估 bmOPN 的生物活性。
方法
我们评估了 bmOPN 的生物活性，包括对肠道生长、免疫反应和大脑发育的影响。在本研究中，野生型（WT）幼鼠由 WT 母鼠、KO 母鼠或 KO 母鼠及其补充物（从出生后第 1 天到第 21 天，即 P1-P21）喂养。
结果
我们的结果表明，口服摄入的 bmOPN 在体内胃肠道消化过程中具有一定的抗性，补充的 bmOPN 对促进小肠生长具有与鼠乳 OPN（mmOPN）相似的作用，通过十二指肠绒毛高度和隐窝深度的组织学分析在 P10 时显示，对 P30 时 LPS 刺激的 TNF-α 反应具有修饰作用，以及通过增加髓鞘相关糖蛋白（MAG）和髓鞘碱性蛋白（MBP）的表达促进大脑髓鞘形成，从而改善认知发育。
结论
我们发现，与 mmOPN 氨基酸序列不同但具有保守整合素结合位点的 bmOPN 发挥与 mmOPN 相似的生物活性，这表明当添加到配方奶粉中时，bmOPN 可能为人乳婴儿提供生物活性。
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