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
文摘目的分析颞下颌关节盘形态、位置与下颌骨垂直向和矢状向形态的关系。方法选择因颞下颌关节紊乱综合征(temporomandibular disorders,TMD)就诊于四川大学华西口腔医院颞下颌关节科的223例成年女性患者。根据核磁共振影像(magnetic resonance imaging,MRI)将关节盘位置分为盘髁关系正常、可复性盘前移(disc displacement with reduction,DDwR)和不可复性盘前移(disc displacement without reduction,DDwoR)3组,关节盘形态分为基本正常和异常两组。根据头颅侧位片测量下颌骨垂直向(下颌平面角、Y轴角、下颌支高度)和矢状向(SNB、下颌体长度、鞍角)形态指标。比较各个测量指标与关节盘位置、形态的相关性。结果关节盘位置和形态与下颌平面角、下颌支高度和Y轴角之间具有相关性(P<0.05),左侧关节盘位置与SNB之间具有相关性(P<0.05),双侧关节盘形态与SNB之间具有相关性(P<0.05)。结论关节盘的形态和位置与下颌骨的垂直向和矢状向形态之间有相关性,与垂直向形态之间的相关性更加密切。
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.
