Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs

Abstract Bone has long been acknowledged as a fundamental structural entity that provides support and protection to the body’s organs. However, emerging research indicates that bone plays a crucial role in the regulation of systemic metabolism. This is achieved through the secretion of a variety of...

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Main Authors: Tailin He, Lei Qin, Sheng Chen, Shaochuan Huo, Jie Li, Fuping Zhang, Weihong Yi, Yifang Mei, Guozhi Xiao
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Bone Research
Online Access:https://doi.org/10.1038/s41413-025-00424-1
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author Tailin He
Lei Qin
Sheng Chen
Shaochuan Huo
Jie Li
Fuping Zhang
Weihong Yi
Yifang Mei
Guozhi Xiao
author_facet Tailin He
Lei Qin
Sheng Chen
Shaochuan Huo
Jie Li
Fuping Zhang
Weihong Yi
Yifang Mei
Guozhi Xiao
author_sort Tailin He
collection DOAJ
description Abstract Bone has long been acknowledged as a fundamental structural entity that provides support and protection to the body’s organs. However, emerging research indicates that bone plays a crucial role in the regulation of systemic metabolism. This is achieved through the secretion of a variety of hormones, cytokines, metal ions, extracellular vesicles, and other proteins/peptides, collectively referred to as bone-derived factors (BDFs). BDFs act as a medium through which bones can exert targeted regulatory functions upon various organs, thereby underscoring the profound and concrete implications of bone in human physiology. Nevertheless, there remains a pressing need for further investigations to elucidate the underlying mechanisms that inform the effects of bone on other body systems. This review aims to summarize the current findings related to the roles of these significant modulators across different organs and metabolic contexts by regulating critical genes and signaling pathways in vivo. It also addresses their involvement in the pathogenesis of various diseases affecting the musculoskeletal system, circulatory system, glucose and lipid metabolism, central nervous system, urinary system, and reproductive system. The insights gained from this review may contribute to the development of innovative therapeutic strategies through a focused approach to bone secretomes. Continued research into BDFs is expected to enhance our understanding of bone as a multifunctional organ with diverse regulatory roles in human health.
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issn 2095-6231
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publishDate 2025-04-01
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series Bone Research
spelling doaj-art-d55a3a418c6f4a59bc3370de1778df852025-08-20T03:52:19ZengNature Publishing GroupBone Research2095-62312025-04-0113112810.1038/s41413-025-00424-1Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organsTailin He0Lei Qin1Sheng Chen2Shaochuan Huo3Jie Li4Fuping Zhang5Weihong Yi6Yifang Mei7Guozhi Xiao8Department of Rheumatology and Immunology, Shenzhen Third People’s HospitalDepartment of Orthopedics, Shenzhen Nanshan People’s Hospital, and the 6th Affiliated Hospital of Shenzhen University Medical SchoolDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyShenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, China, Shenzhen Research Institute of Guangzhou University of Traditional Medicine (Futian)Department of Biochemistry, Homeostatic Medicine Institute, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and TechnologyCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)Department of Orthopedics, Shenzhen Nanshan People’s Hospital, and the 6th Affiliated Hospital of Shenzhen University Medical SchoolDepartment of Rheumatology and Immunology, Shenzhen Third People’s HospitalDepartment of Biochemistry, Homeostatic Medicine Institute, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and TechnologyAbstract Bone has long been acknowledged as a fundamental structural entity that provides support and protection to the body’s organs. However, emerging research indicates that bone plays a crucial role in the regulation of systemic metabolism. This is achieved through the secretion of a variety of hormones, cytokines, metal ions, extracellular vesicles, and other proteins/peptides, collectively referred to as bone-derived factors (BDFs). BDFs act as a medium through which bones can exert targeted regulatory functions upon various organs, thereby underscoring the profound and concrete implications of bone in human physiology. Nevertheless, there remains a pressing need for further investigations to elucidate the underlying mechanisms that inform the effects of bone on other body systems. This review aims to summarize the current findings related to the roles of these significant modulators across different organs and metabolic contexts by regulating critical genes and signaling pathways in vivo. It also addresses their involvement in the pathogenesis of various diseases affecting the musculoskeletal system, circulatory system, glucose and lipid metabolism, central nervous system, urinary system, and reproductive system. The insights gained from this review may contribute to the development of innovative therapeutic strategies through a focused approach to bone secretomes. Continued research into BDFs is expected to enhance our understanding of bone as a multifunctional organ with diverse regulatory roles in human health.https://doi.org/10.1038/s41413-025-00424-1
spellingShingle Tailin He
Lei Qin
Sheng Chen
Shaochuan Huo
Jie Li
Fuping Zhang
Weihong Yi
Yifang Mei
Guozhi Xiao
Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs
Bone Research
title Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs
title_full Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs
title_fullStr Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs
title_full_unstemmed Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs
title_short Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs
title_sort bone derived factors mediate crosstalk between skeletal and extra skeletal organs
url https://doi.org/10.1038/s41413-025-00424-1
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