Senescent immune cells release grancalcin to promote skeletal aging.

Skeletal aging is characterized by low bone turnover and marrow fat accumulation. However, the underlying mechanism for this imbalance is unclear. Here, we show that during aging in rats and mice proinflammatory and senescent subtypes of immune cells, including macrophages and neutrophils, accumulate in the bone marrow and secrete abundant grancalcin. The injection of recombinant grancalcin into young mice was sufficient to induce premature skeletal aging. In contrast, genetic deletion of Gca in neutrophils and macrophages delayed skeletal aging. Mechanistically, we found that grancalcin binds to the plexin-b2 receptor and partially inactivates its downstream signaling pathways, thus repressing osteogenesis and promoting adipogenesis of bone marrow mesenchymal stromal cells. Heterozygous genetic deletion of Plexnb2 in skeletal stem cells abrogated the improved bone phenotype of Gca-knockout mice. Finally, we developed a grancalcin-neutralizing antibody and showed that its treatment of older mice improved bone health. Together, our data suggest that grancalcin could be a potential target for the treatment of age-related osteoporosis. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Chang-Jun Li, Ye Xiao, Yu-Chen Sun, Wen-Zhen He, Ling Liu, Mei Huang, Chen He, Min Huang, Kai-Xuan Chen, Jing Hou, Xu Feng, Tian Su, Qi Guo, Yan Huang, Hui Peng, Mi Yang, Guang-Hui Liu, Xiang-Hang Luo. Senescent immune cells release grancalcin to promote skeletal aging. Cell metabolism. 2021 Oct 05;33(10):1957-1973.e6

Mesh Tags

PMID: 34614408

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