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) 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;Loxl2^(flox/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
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
Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elu...Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.展开更多
检索并分析了PubMed Central (PMC)数据库收录的生物医学期刊的开放获取(Open Access,OA)特征(语种、OA类型、CC协议、同行评议策略、出版商、APC等),并对Scopus收录期刊的CiteScore数据、Web of Science (WoS)收录期刊的JIF数据及发文...检索并分析了PubMed Central (PMC)数据库收录的生物医学期刊的开放获取(Open Access,OA)特征(语种、OA类型、CC协议、同行评议策略、出版商、APC等),并对Scopus收录期刊的CiteScore数据、Web of Science (WoS)收录期刊的JIF数据及发文量进行了可视化和统计学分析。结果显示:PMC数据库收录的105种中国生物医学期刊中,有80种被WoS收录,其中SCIE收录59种,ESCI收录20种,另有1种同时被SCIE和SSCI收录;英文刊占多数(93种,88.57%);采用最多的CC协议是CC BY-NC-ND (40种,38.09%);单盲和双盲同行评议占绝对优势(40.00%vs.47.62%);与国际大型出版商合作办刊是主要的经营特征;在被WoS和Scopus收录的期刊中,即年JIF和5年JIF平均分值为5.2和5.3,CiteScore平均分值为7.6,差异有统计学意义(P<0.000 1);在发文量方面,总体发文量较小,且无巨型OA期刊;APC均值分别为1 963美元,在400~3 500美元区间呈正态分布。践行EQUATOR Network的生物医学研究报告指南及《学术出版透明与最佳行为准则》是生物医学期刊OA高质量发展的保障,单盲的同行评议策略有助于打击学术不端行为。借鉴PMC收录期刊的OA特征及PMC的收录标准,将有助于我国生物学OA期刊的高质量发展。展开更多
文摘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 an NIH grant R01 DE031413 (M.V.B.)。
文摘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;Loxl2^(flox/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.
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).
文摘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.
基金supported by the Anhui Provincial Natural Science Foundation(Grant No.2308085MH250)the Natural Science Research Project of Anhui Educational Committee(Grant No.2023AH053327)the Scientific Research Fund Project of Anhui Medical University(2020xkj039).
文摘Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.
