@article{Zou2024, 
author = {Nan-Yu Zou and Ran Liu and Mei Huang and Yu-Rui Jiao and Jie Wei and Yangzi Jiang and Wen-Zhen He and Min Huang and Yi-Li Xu and Ling Liu and Yu-Chen Sun and Mi Yang and Qi Guo and Yan Huang and Tian Su and Ye Xiao and Wei-Shan Wang and Chao Zeng and Guang-Hua Lei and Xiang-Hang Luo and Chang-Jun Li},
title = {Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing},
year = {2024},
journal = {Bone Research},
volume = {12},
pages = {6},
url = {https://www.sciopen.com/article/10.1038/s41413-023-00309-1},
doi = {10.1038/s41413-023-00309-1},
abstract = {Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.}
}