Osteoarthritis(OA),the most common chronic joint disease,leads to remarkable morbidity and disability.The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of ost...Osteoarthritis(OA),the most common chronic joint disease,leads to remarkable morbidity and disability.The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of osteoarthritic joints is crucial for elucidating OA pathogenesis and facilitating drug development.In this study,we present a microfluidics-based cartilage-on-a-chip model that integrates tunable mechanical stimulation and inter-tissue/cell communication,mimicking the key physiological characteristics of articular cartilage for organ-level OA research.By applying controllable mechanical compression,we established a model that captures healthy and injury hallmarks of the cartilage and directly observed the mechanotransduction responses in chondrocytes.We further demonstrated that mechanically damaged cartilage induces synovial abnormalities and immune dysregulation and explored the potential of our chip as a platform for screening therapeutic targets.This cartilage-on-a-chip offers an in vitro system with a close-to-in vivo microenvironment for investigating complex bio-chemo-mechanical interactions,paving the way for advanced studies on OA pathogenesis and drug screening.展开更多
开放获取(Open Access, OA)是开放科学的核心,高校图书馆作为学术资源枢纽,其 OA 资源建设已从个体行动转向多方协同。本文以“图书馆—图书馆”双人演化博弈与“图书馆—政府—出版社”三方演化博弈为分析框架,揭示协同建设的内在机理...开放获取(Open Access, OA)是开放科学的核心,高校图书馆作为学术资源枢纽,其 OA 资源建设已从个体行动转向多方协同。本文以“图书馆—图书馆”双人演化博弈与“图书馆—政府—出版社”三方演化博弈为分析框架,揭示协同建设的内在机理与稳定条件;结合我国高校图书馆协同建设的现状和困境,从治理机制、技术支撑、资源整合、服务创新、保障体系五大维度提出了针对性的实施路径,最后得出了高校图书馆OA资源协同建设模式。展开更多
Temporomandibular joint osteoarthritis(TMJ-OA) affects a significant proportion of the population worldwide.However,there has been no substantial progress in the development of FDA-approved drugs for treatment due to ...Temporomandibular joint osteoarthritis(TMJ-OA) affects a significant proportion of the population worldwide.However,there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms.Lysyl Oxidase-Like-2(LOXL2) promotes knee joint cartilage protection and is down regulated in a TMJ-OA animal model.We evaluated the role of LOXL2 in TMJ cartilage,its molecular mechanism,and gene networks using in vivo Loxl2 knockout mice(Acan-Cre;Loxl2flox/flox) and ex vivo goat TMJ cartilage.Our results show that Loxl2 knockout in mouse cartilage upregulates Il1b,Mmp9,Mmp13,Adamts4,and Adamts5,but reduces the levels of aggrecan and proteoglycan.Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response,TNFA signaling via NF-κB,extracellular matrix(ECM),and collagen degradation pathway network.Conversely,LOXL2 treatment reduces interleukin-1beta(IL-1β)-induced expression of Mmp13,protects mitochondrial function,and ECM from degeneration.Importantly,LOXL2attenuates IL-1 β-induced chondrocyte apoptosis via the phosphorylation of NF-κB and expression of the pain-related gene PTGS2(encodes COX2).Taken together,Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation,mitochondrial dysfunction,chondrocyte apoptosis,and inflammatory gene expression,whereas LOXL2 treatment mitigate these effects.展开更多
Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,f...Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,function,and mobility in individuals with knee osteoarthritis(OA)?Among 3192 participants,those classified as“Lifelong ST”(n=142)demonstrated superior 4-year patient-reported outcomes and exhibited the lowest incidence of mobility disability(0.8%vs 2.3%-4.1%).Notably,they also maintained the fastest walking speeds at Year 4.展开更多
Temporomandibular joint osteoarthritis(TMJ-OA),the most common degenerative disease of the TMJ,is influenced by various adaptive,inflammatory,and mechanical stressors.In this study,we describe molecular alterations of...Temporomandibular joint osteoarthritis(TMJ-OA),the most common degenerative disease of the TMJ,is influenced by various adaptive,inflammatory,and mechanical stressors.In this study,we describe molecular alterations of the synovium of the articular disk in response to mechanical and inflammatory stimuli.Using an integrated transcriptomic approach combining subcellular spatial transcriptomics and single-cell RNA sequencing in murine models of mechanical stress and articular disk derangement,we characterized synovial changes associated with adipogenesis,fibrosis,and macrophage activation.In addition,cell type–and cluster–specific catabolic changes were observed under these stress conditions,suggesting potential contributions to TMJ-OA onset.These results provide a methodology-oriented resource for investigating the molecular pathology of TMJ disorders and may help guide future studies toward the development of targeted therapeutic strategies.展开更多
基金supported by the National Natural Science Foundation of China(Nos.12072010 and 11674019)the Fundamental Research Funds for the Central Universities(No.YWF22-K-101)the National Key Research and Development Program of China(No.2022YFB3804300).
摘要Osteoarthritis(OA),the most common chronic joint disease,leads to remarkable morbidity and disability.The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of osteoarthritic joints is crucial for elucidating OA pathogenesis and facilitating drug development.In this study,we present a microfluidics-based cartilage-on-a-chip model that integrates tunable mechanical stimulation and inter-tissue/cell communication,mimicking the key physiological characteristics of articular cartilage for organ-level OA research.By applying controllable mechanical compression,we established a model that captures healthy and injury hallmarks of the cartilage and directly observed the mechanotransduction responses in chondrocytes.We further demonstrated that mechanically damaged cartilage induces synovial abnormalities and immune dysregulation and explored the potential of our chip as a platform for screening therapeutic targets.This cartilage-on-a-chip offers an in vitro system with a close-to-in vivo microenvironment for investigating complex bio-chemo-mechanical interactions,paving the way for advanced studies on OA pathogenesis and drug screening.
摘要开放获取(Open Access, OA)是开放科学的核心,高校图书馆作为学术资源枢纽,其 OA 资源建设已从个体行动转向多方协同。本文以“图书馆—图书馆”双人演化博弈与“图书馆—政府—出版社”三方演化博弈为分析框架,揭示协同建设的内在机理与稳定条件;结合我国高校图书馆协同建设的现状和困境,从治理机制、技术支撑、资源整合、服务创新、保障体系五大维度提出了针对性的实施路径,最后得出了高校图书馆OA资源协同建设模式。
基金supported by an NIH grant R01 DE031413 (M.V.B.)。
摘要Temporomandibular joint osteoarthritis(TMJ-OA) affects a significant proportion of the population worldwide.However,there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms.Lysyl Oxidase-Like-2(LOXL2) promotes knee joint cartilage protection and is down regulated in a TMJ-OA animal model.We evaluated the role of LOXL2 in TMJ cartilage,its molecular mechanism,and gene networks using in vivo Loxl2 knockout mice(Acan-Cre;Loxl2flox/flox) and ex vivo goat TMJ cartilage.Our results show that Loxl2 knockout in mouse cartilage upregulates Il1b,Mmp9,Mmp13,Adamts4,and Adamts5,but reduces the levels of aggrecan and proteoglycan.Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response,TNFA signaling via NF-κB,extracellular matrix(ECM),and collagen degradation pathway network.Conversely,LOXL2 treatment reduces interleukin-1beta(IL-1β)-induced expression of Mmp13,protects mitochondrial function,and ECM from degeneration.Importantly,LOXL2attenuates IL-1 β-induced chondrocyte apoptosis via the phosphorylation of NF-κB and expression of the pain-related gene PTGS2(encodes COX2).Taken together,Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation,mitochondrial dysfunction,chondrocyte apoptosis,and inflammatory gene expression,whereas LOXL2 treatment mitigate these effects.
摘要Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,function,and mobility in individuals with knee osteoarthritis(OA)?Among 3192 participants,those classified as“Lifelong ST”(n=142)demonstrated superior 4-year patient-reported outcomes and exhibited the lowest incidence of mobility disability(0.8%vs 2.3%-4.1%).Notably,they also maintained the fastest walking speeds at Year 4.
基金supported by JSPS KAKENHI Grant Numbers 23K27796(to F.Y.),21KK0155(to F.Y.),and JP22H04925(PAGS)(to Y.S.and F.Y.)The Nakatomi Foundation(to K.S.)Young Investigator Award from the American Society for Bone and Mineral Research(to K.S.).
摘要Temporomandibular joint osteoarthritis(TMJ-OA),the most common degenerative disease of the TMJ,is influenced by various adaptive,inflammatory,and mechanical stressors.In this study,we describe molecular alterations of the synovium of the articular disk in response to mechanical and inflammatory stimuli.Using an integrated transcriptomic approach combining subcellular spatial transcriptomics and single-cell RNA sequencing in murine models of mechanical stress and articular disk derangement,we characterized synovial changes associated with adipogenesis,fibrosis,and macrophage activation.In addition,cell type–and cluster–specific catabolic changes were observed under these stress conditions,suggesting potential contributions to TMJ-OA onset.These results provide a methodology-oriented resource for investigating the molecular pathology of TMJ disorders and may help guide future studies toward the development of targeted therapeutic strategies.