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© 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Obesity is associated with skeletal deterioration and increased fracture risk, but the underlying mechanism is unclear. Herein, it is shown that obese gut microbiota promotes skeletal deterioration by inducing bone marrow macrophages (BMMs) senescence and grancalcin (GCA) secretion. Obese mice and those receiving obese fecal microbiota transplants exhibit increased senescent macrophages and elevated GCA expression in the bone marrow. In a study of 40 participants, it is found that obese patients are associated with higher serum GCA levels. It is further revealed that obese gut‐microbiota derived lipopolysaccharides (LPS) stimulate GCA expression in senescent BMMs via activating Toll‐like receptor 4 pathway. Mice with depletion of the Gca gene are resistant to the negative effects of obesity and LPS on bone. Moreover, neutralizing antibody against GCA mitigates skeletal deterioration in obese mice and LPS‐induced chronic inflammation mouse model. The data suggest that the interaction between gut microbiota and the immune system contributes to obesity‐associated skeletal deterioration, and targeting senescent macrophages and GCA shows potential of protecting skeletal health in obese population.

Details

Title
Gut Microbiota Modulates Obesity‐Associated Skeletal Deterioration Through Macrophage Aging and Grancalcin Secretion
Author
Huang, Min 1 ; Huang, Mei 2   VIAFID ORCID Logo  ; Liu, Ling 2 ; Yang, Fang 3 ; He, Chen 2 ; Sun, Yu‐Chen 2 ; Jiao, Yu‐Rui 2 ; Tang, Xiang 2 ; Hou, Jing 2 ; Chen, Kai‐Xuan 2 ; He, Wen‐Zhen 2 ; Wei, Jie 4   VIAFID ORCID Logo  ; Chen, Hui‐Ling 5 ; Li, Xia 6 ; Zeng, Chao 7   VIAFID ORCID Logo  ; Lei, Guang‐Hua 8   VIAFID ORCID Logo  ; Li, Chang‐Jun 9   VIAFID ORCID Logo 

 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital, Central South University, Changsha, China, Department of General Medicine, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, China 
 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital, Central South University, Changsha, China 
 Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China 
 Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China, Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China, Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China, Key Laboratory of Aging‐related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, China 
 Department of Endocrine Subspecialty of Gerontology, Xiangya Hospital, Central South University, Changsha, China 
 Department of General Medicine, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, China 
 Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China, Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China, Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China, Key Laboratory of Aging‐related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, China, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China 
 Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China, Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China, Key Laboratory of Aging‐related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, China, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China 
 Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital, Central South University, Changsha, China, Key Laboratory of Aging‐related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, China, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China, FuRong Laboratory, Changsha, China, Laboratory Animal Center, Xiangya Hospital, Central South University, Changsha, China 
Section
Research Article
Publication year
2025
Publication date
Jul 1, 2025
Publisher
John Wiley & Sons, Inc.
e-ISSN
21983844
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3232671883
Copyright
© 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.