成纤维细胞活化蛋白
骨关节炎
软骨
成纤维细胞
间质细胞
癌症研究
化学
软骨寡聚基质蛋白
类风湿性关节炎
医学
免疫学
内科学
病理
生物化学
体外
解剖
替代医学
癌症
作者
Aoyuan Fan,Guangjie Wu,Jianfang Wang,Liangyu Lu,Jingyi Wang,Hanjing Wei,Yuxi Sun,Yanhua Xu,Chunyang Mo,Xiaoying Zhang,Zhiying Pang,Zhangyi Pan,Yiming Wang,Liangyu Lu,Guojian Fu,Mengqiu Ma,Qiaoling Zhu,Dandan Cao,Jianchun Qin,Feng Yin,Rui Yue
出处
期刊:Bone research
[Springer Nature]
日期:2023-01-02
卷期号:11 (1)
被引量:5
标识
DOI:10.1038/s41413-022-00243-8
摘要
Abstract Fibroblast activation protein (Fap) is a serine protease that degrades denatured type I collagen, α2-antiplasmin and FGF21. Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin (Oln). Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis (RA). However, whether Fap plays a critical role in osteoarthritis (OA) remains poorly understood. Here, we found that Fap is significantly elevated in osteoarthritic synovium, while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice. Mechanistically, we found that Fap degrades denatured type II collagen (Col II) and Mmp13-cleaved native Col II. Intra-articular injection of rFap significantly accelerated Col II degradation and OA progression. In contrast, Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA. Genetic deletion of Oln significantly exacerbated OA progression, which was partially rescued by Fap deletion or inhibition. Intra-articular injection of rOln significantly ameliorated OA progression. Taken together, these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.
科研通智能强力驱动
Strongly Powered by AbleSci AI