| 2 | Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression显示文摘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 r Fap 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 r Oln 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. | Aoyuan Fan Genbin Wu Jianfang Wang Laiya 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 Jiachen Qin Feng Yin Rui Yue | 2023 | Bone Research2023，11，1： | 0 |
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