骨关节炎
前列腺素E2
骨重建
医学
背根神经节
软骨下骨
钠通道
癌症研究
细胞生物学
内科学
内分泌学
化学
背
病理
生物
解剖
钠
关节软骨
替代医学
有机化学
作者
Jianxi Zhu,Gehua Zhen,Shuai An,Xiao Wang,Mei Wan,Yusheng Li,Zhiyong Chen,Yun Guan,Xinzhong Dong,Yihe Hu,Xu Cao
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2020-05-22
卷期号:9
被引量:36
摘要
Pain is the most prominent symptom of osteoarthritis (OA) progression. However, the relationship between pain and OA progression remains largely unknown. Here we report osteoblast secret prostaglandin E2 (PGE2) during aberrant subchondral bone remodeling induces pain and OA progression in mice. Specific deletion of the major PGE2 producing enzyme cyclooxygenase 2 (COX2) in osteoblasts or PGE2 receptor EP4 in peripheral nerve markedly ameliorates OA symptoms. Mechanistically, PGE2 sensitizes dorsal root ganglia (DRG) neurons by modifying the voltage-gated sodium channel Na V 1.8, evidenced by that genetically or pharmacologically inhibiting Na V 1.8 in DRG neurons can substantially attenuate OA. Moreover, drugs targeting aberrant subchondral bone remodeling also attenuates OA through rebalancing PGE2 production and Na V 1.8 modification. Thus, aberrant subchondral remodeling induced Na V 1.8 neuronal modification is an important player in OA and is a potential therapeutic target in multiple skeletal degenerative diseases.
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