Amuc_1473 Links Gut Microbes to Skeletal Homeostasis and Counteracts Multifactorial Osteoporosis

  • Adv Sci (Weinh). 2026 Jun 13:e23067. doi: 10.1002/advs.202523067.
Shan-Shan Rao  1  2  3 ,  Hai-Jin Zeng  1  2 ,  Zun Wang  1  2 ,  Chun-Gu Hong  1  2 ,  Yi-Juan Tan  1  2 ,  Yan-Xin Duan  1  2 ,  Jing-Yao Luo  1  2 ,  Ming-Jie Luo  4 ,  Yi-Wei Liu  1  2 ,  Xin Wang  1  2 ,  Yi Luo  1  2 ,  Teng-Fei Wan  1  2 ,  Yong Zhou  5 ,  Zheng-Guang Wang  5 ,  Guo-Wen Hu  6 ,  Hao Yin  1  2 ,  Xin-Yue Hu  7 ,  Zhen-Xing Wang  1  2  3 ,  Ze-Hui He  1  2 ,  Si-Yi Cheng  8 ,  Wei Du  9 ,  Zhe Guan  1  2 ,  Hai-Li Lang  10 ,  Hong-Ji Liu  1  2 ,  Jia Cao  1  2 ,  Peng Chen  1  2 ,  Jiang-Hua Liu  11 ,  Hui Xie  1  2  3  12 ,  Chun-Yuan Chen  1  2  3
Affiliations
  • 1. Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 2. Hunan Key Laboratory of Angmedicine, Changsha, Hunan, China.
  • 3. National Clinical Research Center For Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 4. Experimental Center of Nursing School, Xinjiang Medical University, Urumqi, Xinjiang, China.
  • 5. Department of Orthopaedics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 6. Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 7. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 8. Department of P.E, Central South University, Changsha, Hunan, China.
  • 9. Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 10. Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 11. Department of Orthopaedics, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
  • 12. FuRong Laboratory, Changsha, Hunan, China.
PMID: 42287124 DOI: 10.1002/advs.202523067
Abstract

Emerging evidence suggests that gut microbiota-derived signals can influence distant organs including the skeleton, yet the key microbial effectors remain elusive. Here, we identify Amuc_1473, a previously uncharacterized protein enriched in extracellular vesicles (EVs) from the commensal bacterium Akkermansia muciniphila (Akk), as a critical mediator of gut-bone communication. Amuc_1473 directly promotes osteogenesis and suppresses osteoclastogenesis by binding to negative elongation factor E (NELF-E) and ribosomal protein L26 (RPL26), regulators of transcriptional pausing and mRNA translation, respectively. Notably, Amuc_1473 levels decline in bone and circulation under diverse pro-osteoporotic conditions-including aging, estrogen deficiency, mechanical unloading, high-fat diet, smoking, alcohol, and chronic stress-paralleling reductions in Akk and its EVs. Intermittent fasting robustly restores Akk abundance, Amuc_1473 levels, and bone quality in these models, via enhanced Mucin production. Our findings establish Amuc_1473 as a microbial effector that systemically regulates bone homeostasis, offering a translatable strategy to prevent or treat multifactorial osteoporosis.

Keywords
akkermansia muciniphila; amuc_1473; extracellular vesicles; intermittent fasting; osteoporosis.
Products