Osteoporosis is a disease of aging, characterized by a decrease in bone quality and a reduction in bone strength. Promoting the activity of osteoblasts is a useful strategy for combating the progression of osteoporosis. As a novel bone growth factor, lactoferrin plays a role in the anabolic activity in bone by inducing the proliferation and differentiation of osteoblasts and inhibiting the formation of osteoclasts. However, potential peptides with osteogenic activity from lactoferrin have not been identified. In the present study, a peptide with osteogenic activity-LFP-C, fragment residues 624 to 632, derived from lactoferrin hydrolysates-was identified using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry and screened using molecular docking analysis. The LFP-C peptide significantly increased the proliferation of mouse cell line MC3T3-E1 and had a promoting effect on alkaline phosphatase activity and calcium deposition. Moreover, LFP-C increased the proportion of osteoblasts in the G2 and M phases. The osteogenic mechanism of LFP-C was also studied by molecular docking. We found that LFP-C could bind to the key domain (Lys13-Thr15-Gln16-Leu17-Gly18-Asp22) of epidermal growth factor receptor, a vital receptor tyrosine kinase that leads to the activation of the mitogen-activated protein kinase pathway. The main interaction forces were interpolated charge, hydrophobicity, and hydrogen bonding. Results indicated that LFP-C may play an osteogenic role in a similar way to lactoferrin, by promoting the proliferation and differentiation of osteoblasts. The findings of this in vitro experiment also demonstrated that the molecular docking method could play a role in the screening process; this in silico approach allowed for faster and cheaper identification of a promising bioactive component.

中文翻译：

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牛乳铁蛋白衍生肽通过调节成骨细胞的增殖和分化诱导成骨。

骨质疏松症是一种衰老性疾病，其特征是骨骼质量下降和骨骼强度下降。促进成骨细胞的活性是对抗骨质疏松症发展的有用策略。乳铁蛋白作为一种新型的骨生长因子，通过诱导成骨细胞的增殖和分化并抑制破骨细胞的形成，在骨的合成代谢活性中发挥作用。然而，尚未发现来自乳铁蛋白的具有成骨活性的潜在肽。在本研究中，使用超高效液相色谱/四极杆飞行时间质谱法鉴定了具有乳源蛋白水解产物的具有成骨活性的肽LFP-C，片段残基624至632，并使用分子对接分析进行了筛选。LFP-C肽显着增加了小鼠细胞系MC3T3-E1的增殖，并对碱性磷酸酶活性和钙沉积具有促进作用。此外，LFP-C增加了G2和M期成骨细胞的比例。还通过分子对接研究了LFP-C的成骨机制。我们发现LFP-C可以与表皮生长因子受体的关键域（Lys13-Thr15-Gln16-Leu17-Gly18-Asp22）结合，这是一种重要的受体酪氨酸激酶，可导致丝裂原活化的蛋白激酶途径的激活。主要的相互作用力是内插电荷，疏水性和氢键。结果表明，LFP-C可能通过促进成骨细胞的增殖和分化，以与乳铁蛋白相似的方式发挥成骨作用。体外实验的结果还表明，分子对接方法可以在筛选过程中发挥作用。这种计算机方法可以更快，更便宜地鉴定有前途的生物活性成分。