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

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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.

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Funding

This work was supported by Jiangmen Science and Technology Program in Basic and Theoretical Science Research (2020-159) and The Postdoctoral Science Foundation of China (2020M672731).

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Authors and Affiliations

  1. Department of Orthopedics, The People’s Hospital of JiangMen, No. 172 Gaodi Li, Pengjiang District, Jiangmen, 529000, Guangdong, China

    Dianshan Ke, Xinwen Wang & Yinquan Lin

  2. Department of Orthopedics, Liuzhou Workers Hospital, No.47, Zone 4, Hongyan Road, Liunan District, Liuzhou, 545005, Guangxi, China

    Shengwang Wei

  3. Academy of Orthopedics in Guangdong Province, The Third Affiliated Hospital, Southern Medical University, Guangzhou, 510630, Guangdong, China

    Dianshan Ke

Authors
  1. Dianshan Ke
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  2. Xinwen Wang
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  3. Yinquan Lin
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  4. Shengwang Wei
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Contributions

DK, YL and SW conceived and designed the overall experiments; DK and SW carried out experiments, analyzed data, and prepared figures; XW assisted in experimental preparation and data analysis; DKand SW wrote the manuscript.

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Correspondence to Yinquan Lin or Shengwang Wei.

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Ke, D., Wang, X., Lin, Y. et al. Lactoferrin promotes the autophagy activity during osteoblast formation via BCL2-Beclin1 signaling. Mol Biol Rep 49, 259–266 (2022). https://doi.org/10.1007/s11033-021-06866-0

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  • DOI: https://doi.org/10.1007/s11033-021-06866-0

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