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
By the analysis of CORBA technology, distributed technology, multi agent, fuzzy cluster, OA system, expert system and decision support technology, a distributed OA expert system model based on fuzzy rules (DOAES) is ...By the analysis of CORBA technology, distributed technology, multi agent, fuzzy cluster, OA system, expert system and decision support technology, a distributed OA expert system model based on fuzzy rules (DOAES) is proposed. In DOAES, the knowledge and experience of decision makers are processed and transferred into the knowledge base. So the system has the adaptive ability and re study function and the decision results are more scientific and more objective. The DOAES is successfully applied in the management system of invest promotion.展开更多
Purpose:This study aimed to assess the influence of older vs.younger age and previous anterior cruciate ligament(ACL)injury on resting serum cartilage oligomeric matrix protein(sCOMP(t_(pre)))concentration,on immediat...Purpose:This study aimed to assess the influence of older vs.younger age and previous anterior cruciate ligament(ACL)injury on resting serum cartilage oligomeric matrix protein(sCOMP(t_(pre)))concentration,on immediate load-induced sCOMP kinetics after a 30-min treadmill walking stress(ΔsCOMP(t_(post))),and on the dose-response relationship between ambulatory load magnitude andΔsCOMP(t_(post)).Methods:A total of 85 participants were recruited in 4 groups(20-30 years:24 healthy,23 ACL-injured;40-60 years:23 healthy,15 ACL-injured).Blood samples were collected immediately before and after a walking stress at 80%,100%,or 120%bodyweight(BW)on 3 test days and analyzed for sCOMP concentration.Linear models were used to estimate the effect of age,knee status(unilateral ACL injury,2-10 years prior),and sex on sCOMP(t_(pre)),ΔsCOMP(t_(post)),and the dose-re sponse between ambulatory load magnitude andΔsCOMP(t_(post)).Results:We found that sCOMP(t_(pre))was 21%higher in older than younger participants(p<0.001)but did not differ between ACL-injured and healthy participants(p=0.632).Also,ΔsCOMP(t_(post))was 19%lower in older than younger participants(p=0.030)and increased with body mass index(p<0.001),sCOMP(t_(pre))(p=0.008),and with 120%BW(p<0.001),independent of age,ACL injury,or sex.Conclusion:Age but not prior ACL injury influences resting sCOMP and load-induced sCOMP.The dose-response relationship between ambulatory load magnitude and load-induced sCOMP changes is not affected by age,ACL injury,or sex.A better understanding of systemic sCOMP and the role of its mechanoresponse for the understanding of osteoarthritis pathophysiology and monitoring intervention efficacy may require knowledge of individual cartilage composition and tissue-level loading parameters.展开更多
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.
文摘By the analysis of CORBA technology, distributed technology, multi agent, fuzzy cluster, OA system, expert system and decision support technology, a distributed OA expert system model based on fuzzy rules (DOAES) is proposed. In DOAES, the knowledge and experience of decision makers are processed and transferred into the knowledge base. So the system has the adaptive ability and re study function and the decision results are more scientific and more objective. The DOAES is successfully applied in the management system of invest promotion.
基金funded by the Swiss National Science Foundation(#184912,in 2019)funding from the German Research Foundation(SFB 1483,in 2021).
文摘Purpose:This study aimed to assess the influence of older vs.younger age and previous anterior cruciate ligament(ACL)injury on resting serum cartilage oligomeric matrix protein(sCOMP(t_(pre)))concentration,on immediate load-induced sCOMP kinetics after a 30-min treadmill walking stress(ΔsCOMP(t_(post))),and on the dose-response relationship between ambulatory load magnitude andΔsCOMP(t_(post)).Methods:A total of 85 participants were recruited in 4 groups(20-30 years:24 healthy,23 ACL-injured;40-60 years:23 healthy,15 ACL-injured).Blood samples were collected immediately before and after a walking stress at 80%,100%,or 120%bodyweight(BW)on 3 test days and analyzed for sCOMP concentration.Linear models were used to estimate the effect of age,knee status(unilateral ACL injury,2-10 years prior),and sex on sCOMP(t_(pre)),ΔsCOMP(t_(post)),and the dose-re sponse between ambulatory load magnitude andΔsCOMP(t_(post)).Results:We found that sCOMP(t_(pre))was 21%higher in older than younger participants(p<0.001)but did not differ between ACL-injured and healthy participants(p=0.632).Also,ΔsCOMP(t_(post))was 19%lower in older than younger participants(p=0.030)and increased with body mass index(p<0.001),sCOMP(t_(pre))(p=0.008),and with 120%BW(p<0.001),independent of age,ACL injury,or sex.Conclusion:Age but not prior ACL injury influences resting sCOMP and load-induced sCOMP.The dose-response relationship between ambulatory load magnitude and load-induced sCOMP changes is not affected by age,ACL injury,or sex.A better understanding of systemic sCOMP and the role of its mechanoresponse for the understanding of osteoarthritis pathophysiology and monitoring intervention efficacy may require knowledge of individual cartilage composition and tissue-level loading parameters.
