The objectives of this study were to （1） determine the distribution and synthesis of pericellular matrix （PCM） molecules （collagen VI, collagen IV and laminin） in rat temporomandibular joint （TMJ） and （2） in...The objectives of this study were to （1） determine the distribution and synthesis of pericellular matrix （PCM） molecules （collagen VI, collagen IV and laminin） in rat temporomandibular joint （TMJ） and （2） investigate the effects of PCM molecules on chondrocytes against inflammation in osteoarthritis. Four zones （fibrous, proliferating, mature and hypertrophic） of condylar cartilage and three bands （anterior, intermediate and posterior） of disc were analysed by immunohistochemistry for the presence of PCM molecules in rat TMJs. Isolated chondrocytes were pre-treated with PCM molecules before being subjected to interleukin （IL）-II~ treatment to stimulate inflammation. The responses of the chondrocytes were analysed using gene expression, nitric oxide release and matrix metalloproteinase （MMP）-13 production measures. Histomorphometric analyses revealed that the highest areal deposition of collagen VI （67.4%）, collagen IV （45.7%） and laminin （52.4%） was in the proliferating zone of TMJ condylar cartilage. No significant difference in the distribution of PCM molecules was noted among the three bands of the TMJ disc. All three PCM molecules were expressed intracellularly by chondrocytes cultured in the monolayer. Among the PCM molecules, pre-treatment with collagen VI enhanced cellular proliferation, ameliorated IL-lp-induced MMP-3, MMP-9, MMP-13 and inducible nitric oxide synthase gene expression, and attenuated the downregulation of cartilage matrix genes, including collagen I, aggrecan and cartilage oligomeric matrix protein （COMP）. Concurrently, collagen VI pretreatment inhibited nitric oxide and MMP-13 production. Our study demonstrates for the first time the distribution and role of PCM molecules, particularly collagen VI, in the protection of chondrocytes against inflammation.展开更多
Test of consistency is critical for the analytic hierarchy process(AHP) methodology. When a pairwise comparison matrix(PCM) fails the consistency test, the decision maker(DM) needs to make revisions. The state of the ...Test of consistency is critical for the analytic hierarchy process(AHP) methodology. When a pairwise comparison matrix(PCM) fails the consistency test, the decision maker(DM) needs to make revisions. The state of the art focuses on changing a single entry or creating a new matrix based on the original inconsistent matrix so that the modified matrix can satisfy the consistency requirement. However, we have noticed that the reason that causes inconsistency is not only numerical inconsistency, but also logical inconsistency, which may play a more important role in the whole inconsistency. Therefore, to realize satisfactory consistency, first of all, we should change some entries that form a directed circuit to make the matrix logically consistent, and then adjust other entries within acceptable deviations to make the matrix numerically consistent while preserving most of the original comparison information. In this paper, we firstly present some definitions and theories, based on which two effective methods are provided to identify directed circuits. Four optimization models are proposed to adjust the original inconsistent matrix. Finally, illustrative examples and comparison studies show the effectiveness and feasibility of our method.展开更多
Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’dir...Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS.展开更多
基金supported by grants from the National University Healthcare System(R221000077733)the National University of Singapore(R221000090112)
文摘The objectives of this study were to （1） determine the distribution and synthesis of pericellular matrix （PCM） molecules （collagen VI, collagen IV and laminin） in rat temporomandibular joint （TMJ） and （2） investigate the effects of PCM molecules on chondrocytes against inflammation in osteoarthritis. Four zones （fibrous, proliferating, mature and hypertrophic） of condylar cartilage and three bands （anterior, intermediate and posterior） of disc were analysed by immunohistochemistry for the presence of PCM molecules in rat TMJs. Isolated chondrocytes were pre-treated with PCM molecules before being subjected to interleukin （IL）-II~ treatment to stimulate inflammation. The responses of the chondrocytes were analysed using gene expression, nitric oxide release and matrix metalloproteinase （MMP）-13 production measures. Histomorphometric analyses revealed that the highest areal deposition of collagen VI （67.4%）, collagen IV （45.7%） and laminin （52.4%） was in the proliferating zone of TMJ condylar cartilage. No significant difference in the distribution of PCM molecules was noted among the three bands of the TMJ disc. All three PCM molecules were expressed intracellularly by chondrocytes cultured in the monolayer. Among the PCM molecules, pre-treatment with collagen VI enhanced cellular proliferation, ameliorated IL-lp-induced MMP-3, MMP-9, MMP-13 and inducible nitric oxide synthase gene expression, and attenuated the downregulation of cartilage matrix genes, including collagen I, aggrecan and cartilage oligomeric matrix protein （COMP）. Concurrently, collagen VI pretreatment inhibited nitric oxide and MMP-13 production. Our study demonstrates for the first time the distribution and role of PCM molecules, particularly collagen VI, in the protection of chondrocytes against inflammation.
基金supported by the National Natural Science Foundation of China(61601501 61502521)
文摘Test of consistency is critical for the analytic hierarchy process(AHP) methodology. When a pairwise comparison matrix(PCM) fails the consistency test, the decision maker(DM) needs to make revisions. The state of the art focuses on changing a single entry or creating a new matrix based on the original inconsistent matrix so that the modified matrix can satisfy the consistency requirement. However, we have noticed that the reason that causes inconsistency is not only numerical inconsistency, but also logical inconsistency, which may play a more important role in the whole inconsistency. Therefore, to realize satisfactory consistency, first of all, we should change some entries that form a directed circuit to make the matrix logically consistent, and then adjust other entries within acceptable deviations to make the matrix numerically consistent while preserving most of the original comparison information. In this paper, we firstly present some definitions and theories, based on which two effective methods are provided to identify directed circuits. Four optimization models are proposed to adjust the original inconsistent matrix. Finally, illustrative examples and comparison studies show the effectiveness and feasibility of our method.
基金This work was supported by grants from the NIH(DK46635,HL18645 and DK53004)the JDRF(The Center for Translational Research at BRI)PLB is supported by NIH K-08 grant DK080178-01 and an NIH LRP grant.The authors would like to thank Nathan Standifer and Michael Kinsella for their helpful comments and Tuan Nguyen for tissue processing.
文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS.
