脂解
骨髓
内分泌学
淋巴细胞生成
内科学
造血
间充质干细胞
脂肪组织
免疫系统
细胞生物学
化学
生物
干细胞
免疫学
医学
作者
Hui Peng,Biao Hu,Ling-Qi Xie,Tian Su,Changjun Li,Ya Liu,Mingzhi Yang,Ye Xiao,Feng Xu,Rui Zhou,Qi Guo,Zhou Huang,Yan Huang,Jiang Tong,Xiang‐Hang Luo
出处
期刊:Cell Metabolism
[Elsevier]
日期:2022-08-01
卷期号:34 (8): 1168-1182.e6
被引量:31
标识
DOI:10.1016/j.cmet.2022.05.009
摘要
Exercise can prevent osteoporosis and improve immune function, but the mechanism remains unclear. Here, we show that exercise promotes reticulocalbin-2 secretion from the bone marrow macrophages to initiate bone marrow fat lipolysis. Given the crucial role of lipolysis in exercise-stimulated osteogenesis and lymphopoiesis, these findings suggest that reticulocalbin-2 is a pivotal regulator of a local adipose-osteogenic/immune axis. Mechanistically, reticulocalbin-2 binds to a functional receptor complex, which is composed of neuronilin-2 and integrin beta-1, to activate a cAMP-PKA signaling pathway that mobilizes bone marrow fat via lipolysis to fuel the differentiation and function of mesenchymal and hematopoietic stem cells. Notably, the administration of recombinant reticulocalbin-2 in tail-suspended and old mice remarkably decreases bone marrow fat accumulation and promotes osteogenesis and lymphopoiesis. These findings identify reticulocalbin-2 as a novel mechanosensitive lipolytic factor in maintaining energy homeostasis in bone resident cells, and it provides a promising target for skeletal and immune health.
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