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

Mol Biol Rep. 2022 Jan;49(1):259-266. doi: 10.1007/s11033-021-06866-0. Epub 2021 Oct 29.

Abstract

Background: 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.

Methods and results: 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.

Conclusions: In conclusion, lactoferrin can inhibit BCL2 expression in osteoblasts, further enhancing Beclin1-dependent autophagy activation.

Keywords: Autophagy; BCL2; Beclin1; Lactoferrin; Osteoblasts.

MeSH terms

  • Animals
  • Autophagy
  • Beclin-1 / genetics*
  • Beclin-1 / metabolism
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Gene Knockdown Techniques
  • Lactoferrin / metabolism*
  • Osteoblasts / cytology*
  • Osteoblasts / metabolism
  • Osteogenesis
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Signal Transduction

Substances

  • Bcl2 protein, rat
  • Beclin-1
  • Becn1 protein, rat
  • Biomarkers
  • Proto-Oncogene Proteins c-bcl-2
  • Lactoferrin