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REVIEW article

Front. Endocrinol.

Sec. Bone Research

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1660312

This article is part of the Research TopicMolecular and Cellular Mechanisms of Bone RemodelingView all 4 articles

Review Direct and indirect regulation of bone metabolism by lactoferrin

Provisionally accepted
  • 1Shandong Second Medical University, Weifang, China
  • 2Jining No.1 People's Hospital, Jining, China

The final, formatted version of the article will be published soon.

Lactoferrin exerts positive regulation on bone metabolism through both direct and indirect pathways. Directly, it modulates osteoblasts, osteoclasts, and chondrocytes via factors such as insulin-like growth factor (IGF), low-density lipoprotein receptor-associated protein (LRP), transforming growth factor β (TGF-β) receptor, and bone morphogenetic proteins (BMPs). These factors promote differentiation and inhibit apoptosis of bone metabolism-related cells through signaling pathways including the receptor activator of nuclear factor kappa-B (RANK), its ligand RANKL, and osteoprotegerin (OPG) , nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), macrophage colony-stimulating factor (M-CSF), Ca2+, phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), Wnt/β-catenin, BMP-2/Smad, and TGF-β. Indirectly, lactoferrin influences skeletal muscle, energy metabolism, intestinal microbiota, immune function, and calcium-phosphorus homeostasis, all of which positively affect bone metabolism. In-depth research into lactoferrin-derived peptides and their complexes for slow-release systems may open new avenues for treating orthopedic diseases. However, the mechanisms by which lactoferrin regulates bone metabolism remain incompletely understood. This review aims to summarize these mechanisms and highlight recent advances in lactoferrin-derived peptides and their complexed slow-release systems, providing a comprehensive basis for exploring lactoferrin as a potential therapeutic target in bone diseases.

Keywords: Lactoferrin, bone metabolism, Osteoblasts, Osteoclasts, Osteoporosis

Received: 09 Jul 2025; Accepted: 29 Sep 2025.

Copyright: © 2025 Wu, Lv and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Chaoliang Lv, lvchaolianggk@163.com
Cunxin Zhang, zhangcunxin2015@163.com

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