炎症
兰克尔
神经生长因子
医学
骨重建
骨保护素
骨关节炎
骨吸收
软骨
祖细胞
内分泌学
内科学
癌症研究
受体
病理
细胞生物学
干细胞
解剖
生物
激活剂(遗传学)
替代医学
作者
Lan Zhao,Yumei Lai,Hongli Jiao,Jian Huang
标识
DOI:10.1038/s41467-024-47633-6
摘要
Abstract Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. Recent clinical trials of the nerve growth factor (NGF) inhibitors in OA patients have suggested adverse effects of NGF inhibition on joint structure. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNFα to attenuate NF-κB activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression in mice. NGFR deficiency hyper-activates NF-κB in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-κB activation. Together, this study suggests a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.
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