Department of Orthopedics, The People's Hospital of JiangMen, No. 172 Gaodi Li, Pengjiang District, Jiangmen, 529000, Guangdong, China.
Academy of Orthopedics in Guangdong Province, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, Guangdong, China.
Mol Biol Rep. 2022 Jan;49(1):259-266. doi: 10.1007/s11033-021-06866-0. Epub 2021 Oct 29.
Lactoferrin, as the main component of milk, can maintain osteoblast formation, which is conducive to the prevention and treatment of osteoporosis. Lactoferrin also serves as an autophagy regulator, especially in osteoblasts. This study aimed to explore the significance of autophagy in osteoblast formation regulated by lactoferrin and the internal mechanism.
In this study, we firstly explored the roles of lactoferrin in the autophagy activity of primary osteoblasts (LC3 transformation rate, autophagosome formation). Subsequently, we further investigated the effects of lactoferrin on the BCL2 expression and BCL2-Beclin1 complex. Ultimately, the significance of BCL2 overexpression and Beclin1 silencing on lactoferrin-regulated osteoblast autophagy and osteogenic parameters (ALP activity and mRNA expression of PCNA, Col1, BGLAP and OPN) was observed by gene processing, respectively. Our results showed that lactoferrin enhanced the autophagy activity of osteoblasts. Importantly, lactoferrin inhibited BCL2 expression and the co-immunoprecipitation of BCL2 and Beclin1 in osteoblasts. Moreover, lactoferrin-promoted autophagy and osteogenic parameters was reversed by BCL2 overexpression or Beclin1 silencing in osteoblasts.
In conclusion, lactoferrin can inhibit BCL2 expression in osteoblasts, further enhancing Beclin1-dependent autophagy activation.
乳铁蛋白作为牛奶的主要成分，可以维持成骨细胞的形成，有利于骨质疏松症的防治。乳铁蛋白还作为自噬调节剂，特别是在成骨细胞中。本研究旨在探讨乳铁蛋白调节成骨细胞形成中自噬的意义及其内在机制。
本研究首先探讨了乳铁蛋白对原代成骨细胞自噬活性（LC3 转化率、自噬体形成）的作用。随后，我们进一步研究了乳铁蛋白对 BCL2 表达和 BCL2-Beclin1 复合物的影响。最后，通过基因处理分别观察了 BCL2 过表达和 Beclin1 沉默对乳铁蛋白调节成骨细胞自噬和成骨参数（碱性磷酸酶活性和 PCNA、Col1、BGLAP 和 OPN 的 mRNA 表达）的意义。结果表明，乳铁蛋白增强了成骨细胞的自噬活性。重要的是，乳铁蛋白抑制了成骨细胞中 BCL2 的表达和 BCL2 与 Beclin1 的共免疫沉淀。此外，在成骨细胞中，BCL2 过表达或 Beclin1 沉默逆转了乳铁蛋白促进的自噬和成骨参数。
总之，乳铁蛋白可以抑制成骨细胞中 BCL2 的表达，进一步增强 Beclin1 依赖性自噬激活。
