Lactoferrin promotes the autophagy activity during osteoblast formation via BCL2-Beclin1 signaling.

Dianshan Ke,Shengwang Wei,Yinquan Lin,Xinwen Wang

doi:10.1007/s11033-021-06866-0

Abstract

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.

Highlights

Lactoferrin is a kind of iron-binding glycoprotein, which exists in milk, breast milk secretion and so on [1]
These results supported that lactoferrin could stimulate the autophagy activity of osteoblasts
Autophagy plays an indispensable role in the osteoblast formation [10,11,12,13,14], which provides us with an interesting scientific question, how lactoferrin affect the autophagy of osteoblasts

Summary

Introduction

Lactoferrin is a kind of iron-binding glycoprotein, which exists in milk, breast milk secretion and so on [1]. Lactoferrin can promote the osteoblast formation and subsequent osteogenesis, whereby improving pathological bone loss [2,3,4]. Chen et al and Li et al proved that bovine lactoferrin significantly improved bone mass and bone microstructure in ovariectomized rats [5, 6]. Both bovine lactoferrin and human lactoferrin can efficiently promote the proliferation of osteoblast cell line, MC3T3-E1 [7]. Lactoferrin can improve the inhibition of osteogenesis induced by aging through IGF1 signaling [5]. Lactoferrin promotes bone formation of primary osteoblasts, MC3T3-E1 cells in vitro and C57BL/6J mice in vivo [6]. Similar results were reported in other studies [4, 8, 9]

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