衰老
骨髓
内分泌学
内科学
PI3K/AKT/mTOR通路
细胞生物学
骨重建
生物
癌症研究
医学
信号转导
作者
Ling‐Qi Xie,Yalun Cheng,Biao Hu,Baoxiang Pan,Yuze An,Zhuying Xia,Guangping Cai,Changjun Li,Hui Peng
标识
DOI:10.1038/s41413-024-00337-5
摘要
Bone marrow adipocytes (BMAds) affect bone homeostasis, but the mechanism remains unclear. Here, we showed that exercise inhibited PCNA clamp-associated factor (PCLAF) secretion from the bone marrow macrophages to inhibit BMAds senescence and thus alleviated skeletal aging. The genetic deletion of PCLAF in macrophages inhibited BMAds senescence and delayed skeletal aging. In contrast, the transplantation of PCLAF-mediated senescent BMAds into the bone marrow of healthy mice suppressed bone turnover. Mechanistically, PCLAF bound to the ADGRL2 receptor to inhibit AKT/mTOR signaling that triggered BMAds senescence and subsequently spread senescence among osteogenic and osteoclastic cells. Of note, we developed a PCLAF-neutralizing antibody and showed its therapeutic effects on skeletal health in old mice. Together, these findings identify PCLAF as an inducer of BMAds senescence and provide a promising way to treat age-related osteoporosis.
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