Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression

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.

新型乳化体系及其在化妆品中的应用(IV)——多重乳液

多重乳液是一种乳状液(水包油型乳液或油包水型乳液)分散于另外一种连续相(油相或水相)中形成的水包油型乳液和油包水型乳液共存的复杂体系。多重乳液不但兼具了水包油型乳液和油包水型乳液的优势,而且具有独特的“三相两膜”的结构,使其在化妆品、医药、食品、材料等领域中展现出广阔的应用前景。本文首先介绍了多重乳液及其制备方法,总结了影响多重乳液稳定性的因素;概括了多重乳液在化妆品领域的应用优势,包括对功效成分的保护、隔离、缓释、促渗等。在此基础上,阐述了多重乳液在化妆品领域的研究现状,并对目前已报道的特殊多重乳液进行了介绍。最后,对现阶段多重乳液在化妆品领域实际应用中存在的问题及后续应该研究的重点及方向提出了个人看法,旨在为性能优异的多重乳在化妆品领域的实际应用提供依据,也为性能优异的化妆品的开发及活性成分的有效应用提供参考。