Matrix metalloproteinases(MMPs),coupled with other proteinases and glycanases,can degrade proteoglycans,collagens,and other extracellular matrix(ECM)components in inflammatory and non-inflammatory arthritis,making the...Matrix metalloproteinases(MMPs),coupled with other proteinases and glycanases,can degrade proteoglycans,collagens,and other extracellular matrix(ECM)components in inflammatory and non-inflammatory arthritis,making them important pathogenic molecules and ideal disease indicators and pharmaceutical intervention triggers.For MMP responsiveness,MMP-sensitive peptides(MSPs)are among the most easily synthesized and cost-effective substrates,with free ter-minal amine and/or carboxyl groups extensively employed in multiple designs.We hereby provide a comprehensive review over the mechanisms and advances in MSP applications for the management of arthritis.These applications include early and precise diagnosis of MMP activity via fluorescence probe technologies;acting as nanodrug carriers to enable on-demand drug release triggered by pathological microenvironments;and facilitating cartilage engineering through MMP-mediated degradation,which promotes cell migration,matrix synthesis,and tissue integration.Specifically,the ultra-sensitive MSP diagnostic probes could significantly advance the early diagnosis and detection of osteoarthritis(OA),while MSP-based drug carriers for rheumatoid arthritis(RA)can intelligently release antiinflammatory drugs effectively during flare-ups,or even before symptoms manifest.The continuous progress in MSP development may acceleratedly lead to novel management regimens for arthropathy in the future.展开更多
基金jointly supported by National Key R&D Program of China(2023YFB4606700)the National Natural Science Foundation of China(82272561)+2 种基金Sichuan Science and Technology Program(2024NSFSC0002)“1.3.5”Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD23037)China Post-doctoral Science Foundation(2024M752242).
文摘Matrix metalloproteinases(MMPs),coupled with other proteinases and glycanases,can degrade proteoglycans,collagens,and other extracellular matrix(ECM)components in inflammatory and non-inflammatory arthritis,making them important pathogenic molecules and ideal disease indicators and pharmaceutical intervention triggers.For MMP responsiveness,MMP-sensitive peptides(MSPs)are among the most easily synthesized and cost-effective substrates,with free ter-minal amine and/or carboxyl groups extensively employed in multiple designs.We hereby provide a comprehensive review over the mechanisms and advances in MSP applications for the management of arthritis.These applications include early and precise diagnosis of MMP activity via fluorescence probe technologies;acting as nanodrug carriers to enable on-demand drug release triggered by pathological microenvironments;and facilitating cartilage engineering through MMP-mediated degradation,which promotes cell migration,matrix synthesis,and tissue integration.Specifically,the ultra-sensitive MSP diagnostic probes could significantly advance the early diagnosis and detection of osteoarthritis(OA),while MSP-based drug carriers for rheumatoid arthritis(RA)can intelligently release antiinflammatory drugs effectively during flare-ups,or even before symptoms manifest.The continuous progress in MSP development may acceleratedly lead to novel management regimens for arthropathy in the future.
