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衰老的免疫细胞释放颗粒钙蛋白促进骨骼衰老
作者:小柯机器人 发布时间:2021/9/12 13:44:38

中南大学罗湘杭团队发现,衰老的免疫细胞释放颗粒钙蛋白促进骨骼衰老。这一研究成果于2021年9月9日在线发表在国际学术期刊《细胞—代谢》上。

研究人员表明,在大鼠和小鼠的衰老过程中,促炎症和衰老的免疫细胞亚型(包括巨噬细胞和中性粒细胞)在骨髓中积累,并分泌大量的颗粒钙蛋白(grancalcin)。向年轻小鼠注射重组grancalcin足以诱发骨骼过早衰老。相反,中性粒细胞和巨噬细胞中Gca的基因缺失会延迟骨骼的老化。

从机理上讲,研究人员发现grancalcin与plexin-b2受体结合,并部分失活其下游信号通路,从而抑制骨质生成,促进骨髓间质细胞的脂肪生成。骨骼干细胞中plexnb2的杂合遗传缺失废除了Gca基因敲除小鼠的骨骼表型改善。

最后,研究人员开发了一种grancalcin中和抗体,并显示其对老年小鼠的治疗能改善骨骼健康。总之,这些数据表明,grancalcin可能是治疗与年龄有关的骨质疏松症的一个潜在靶标。

据悉,骨骼老化的特点是骨转换率低和骨髓脂肪堆积。然而,这种不平衡的基本机制尚不清楚。

附:英文原文

Title: Senescent immune cells release grancalcin to promote skeletal aging

Author: 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

Issue&Volume: 2021-09-09

Abstract: Skeletal aging is characterized by low bone turnover and marrow fat accumulation.However, the underlying mechanism for this imbalance is unclear. Here, we show thatduring aging in rats and mice proinflammatory and senescent subtypes of immune cells,including macrophages and neutrophils, accumulate in the bone marrow and secrete abundantgrancalcin. The injection of recombinant grancalcin into young mice was sufficientto induce premature skeletal aging. In contrast, genetic deletion of Gca in neutrophils and macrophages delayed skeletal aging. Mechanistically, we foundthat grancalcin binds to the plexin-b2 receptor and partially inactivates its downstreamsignaling pathways, thus repressing osteogenesis and promoting adipogenesis of bonemarrow 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 showedthat its treatment of older mice improved bone health. Together, our data suggestthat grancalcin could be a potential target for the treatment of age-related osteoporosis.

DOI: 10.1016/j.cmet.2021.08.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00372-7

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx