Articular cartilage is a connective tissue consisting of a specialized extracellular matrix （ECM） that dominates the bulk of its wet and dry weight. Type Ⅱ collagen and aggrecan are the main ECM proteins in cartila...Articular cartilage is a connective tissue consisting of a specialized extracellular matrix （ECM） that dominates the bulk of its wet and dry weight. Type Ⅱ collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type Ⅳ, Ⅵ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢ, and ⅩⅣ, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.展开更多
用Ⅱ型胶原免疫注射 DBA/1J 小鼠,3周后用同样方法再注射,4周开始分别投与通痹灵和消炎痛。在投药12周内,观察各组四肢关节炎发病程度,16周后小鼠骨关节作 X 线片和病理组织切片,Ⅱ型胶原抗体价测定用酶结合免疫法,并检查各组血液常规...用Ⅱ型胶原免疫注射 DBA/1J 小鼠,3周后用同样方法再注射,4周开始分别投与通痹灵和消炎痛。在投药12周内,观察各组四肢关节炎发病程度,16周后小鼠骨关节作 X 线片和病理组织切片,Ⅱ型胶原抗体价测定用酶结合免疫法,并检查各组血液常规、肝肾功能等。结果表明通痹灵组与阳性组和消炎痛组相比较,该药对胶原关节炎发病,血中Ⅱ型胶原抗体价和白细胞的增加,四肢关节骨破坏等病变均有显著抑制。血液常规和肝肾功能等检查均未见异常。提示本药不仅具有抗炎和免疫调节作用,而且副作用比较少。展开更多
The therapeutic actions of Qing Luo Yin (QLY清络饮) with heat property and Wen Luo Yin (WLY温络饮) with cold property on pain, swelling of the ankle, arthritis index and ultrastructures of synoviocytes were compared i...The therapeutic actions of Qing Luo Yin (QLY清络饮) with heat property and Wen Luo Yin (WLY温络饮) with cold property on pain, swelling of the ankle, arthritis index and ultrastructures of synoviocytes were compared in rats of type II collagen-induced arthritis (CIA), with tripterygium glycosidorum (TG) used as control. The results indicated that both QLY and WLY could reduce pain, swelling of the ankle and the arthritis index of CIA, and QLY had better effects in reducing the swelling of the ankle and controlling the secondary pathological lesions as compared with WLY. Investigation on the ultrastructures of synoviocytes indicated that both QLY and WLY could reduce the number of Golgi apparatus, rough surface endoplasmic reticulum, dense bodies, matrix filaments and vacuoles so as to suppress the excessive secretion of synoviocytes in rats of CIA.展开更多
Objective: Rheumatoid arthritis(RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction(HGWD) is traditional Chinese medi...Objective: Rheumatoid arthritis(RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction(HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis(CIA) mouse model.Methods: DBA/1J female mice were used to establish the collagen-induced arthritis(CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay(ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors m RNA and protein levels after HGWD intervention in RAW264.7 cells.Results: HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints,reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function.HGWD decreased the expression of m RNA for inflammatory factors and the protein expression levels of p-NF-ΚB and IL-17.Conclusion: These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.展开更多
Summary:Huai Qi Huang(HQH)exerts great effects in clinic,such as anti-inflammation,immune-regulation,anti-cancer,and so on.However,the mechanism by which HQH protects juvenile idiopathic arthritis(JIA)is obscure.Thus,...Summary:Huai Qi Huang(HQH)exerts great effects in clinic,such as anti-inflammation,immune-regulation,anti-cancer,and so on.However,the mechanism by which HQH protects juvenile idiopathic arthritis(JIA)is obscure.Thus,we explored deeply the protective mechanisms in juvenile collagen-induced arthritis(CIA)rat model.Pyroptosis is Gasdermin D(GSDMD)-dependent programmed cell death,involved in many diseases,such as sepsis.We investigated whether GSDMD-induced pyroptosis take part in mechanisms of juvenile CIA arthritis.Juvenile Wistar rats(3-4 weeks)were injected intradermally with fully emulsified bovine typeⅡcollagen and complete Freund's adjuvant to establish CIA rat models.Later,the CIA rats received oral administration of HQH(4.16 g/kg)once a day from the day 21 of modeling,with the treatment lasting for 28 days.Varieties of indicators were measured for evaluation of anti-inflammation effect of HQH,including hind paw swelling,arthritis scores,micro CT,and histopathological changes and the level of pro-inflammatory cytokines in the serum,including tumor necrosis factor alpha(TNF-α)and interleukin-18(IL-18).The expression of GSDMD and caspasein the joint synovial tissues was detected.The results demonstrated that the expression of the pyroptotic protein GSDMD and its upstream caspase-1 was significantly increased in the synovial tissues of CIA rats.The treatment of HQH ameliorated the symptoms in CIA rats,reduced levels of pro-inflammatory cytokines and hind paw swelling,down-regulated the expression of GDSMD and caspase-1.GSDMDinduced pyroptosis participated in the pathogenesis of CIA rats.The study supported that HQH can effectively improve joints inflammation of juvenile collagen-induced arthritis rats by inhibiting pyroptosis pathway in the joint synovial tissues.展开更多
Rheumatoid arthritis(RA)is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation,posing challenges in the development of effective treatments.Nuciferine,an alkaloid found in lo...Rheumatoid arthritis(RA)is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation,posing challenges in the development of effective treatments.Nuciferine,an alkaloid found in lotus leaf,has shown promising anti-inflammatory and anti-tumor effects,yet its efficacy in RA treatment remains unexplored.This study investigated the antiproliferative effects of nuciferine on the MH7A cell line,a human RA-derived fibroblast-like synoviocyte,revealing its ability to inhibit cell proliferation,promote apoptosis,induce apoptosis,and cause G1/S phase arrest.Additionally,nuciferine significantly reduced the migration and invasion capabilities of MH7A cells.The therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis(CIA)rat model,where it markedly alleviated joint swelling,synovial hyperplasia,cartilage injury,and inflammatory infiltration.Nuciferine also improved collagen-induced bone erosion,decreased pro-inflammatory cytokines and serum immunoglobulins(IgG,IgG1,IgG2a),and restored the balance between T helper(Th)17 and regulatory T cells in the spleen of CIA rats.These results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.展开更多
Objective:To demonstrate the rheumatoid arthritis(RA)mechanisms by determining the biochemical changes.To investigate the therapeutic mechanism of moxibustion in RA-model rats using a gas chromatography-mass spectrome...Objective:To demonstrate the rheumatoid arthritis(RA)mechanisms by determining the biochemical changes.To investigate the therapeutic mechanism of moxibustion in RA-model rats using a gas chromatography-mass spectrometry(GC-MS)metabolomics approach.Methods:A total of 24 rats were divided into three groups as follows:normal control group,model group and moxibustion group.Rats in model group and moxibustion group were set up collagen-induced arthritis(CIA)model.Rats in moxibustion group were treated by moxibustion.After 3 weeks of intervention,right ankle joint,serum and articular synovium samples were collected.Right ankle joint samples were used for histopathological evaluation between 3 groups to get the pathological changes of tissues and cells.Serum and articular synovium samples were used to analyze the changed metabolites of moxibustion on RA rats by the GC-MS based metabolomics.Results:Treatment of moxibustion not only significantly increased the weight of CIA rats,reduced the swelling of hind paw,arthritic scores,IL-1β,TNF-αbut also improved histopathological evaluation in right ankle joint samples.Sixteen significantly altered metabolites were found in RA rats as potential biomarkers of arthritis.Thirteen metabolites,significantly adjusted by moxibustion to help relieve arthritis,were selected out as biomarkers of antiarthritic mechanism of moxibustion,which were mainly involved in phenylalanine,tyrosine and tryptophan biosynthesis,glycine,serine and threonine metabolism,phenylalanine metabolism,alanine,aspartate and glutamate metabolism,glyoxylate and dicarboxylate metabolism and aminoacyl-tRNA biosynthesis.Conclusions:We have indicated moxibustion treatment is able to resist inflammation in CIA rats effectively.Using GC-MS metabolomics technique,we detect novel metabolites in the moxibustion antiarthritic process,which may aid in advanced understanding of arthritis and therapeutic mechanism of moxibustion.展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease.It is known that aucubin(AU)exerts anti-inflammatory activity,but its effects and mechanisms in RA are unclear.This study investigated the anti-infl...Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease.It is known that aucubin(AU)exerts anti-inflammatory activity,but its effects and mechanisms in RA are unclear.This study investigated the anti-inflammatory effects and mechanisms of AU in vivo and in vitro.Human fibroblast-like synoviocyte cells from patients with RA(HFLS-RA),RAW264.7 cells,and MC3T3-E1 cells were used to evaluate the effects of AU on migration,invasion,apoptosis,osteoclast differentiation and production.Immunofluorescence was used to observe nuclear translocation of nuclear factor(NF)-/cB,the double luciferase reporter gene method was used to observe NF-/cB-p65 activity in AU-treated MC3T3-E1 cells.RT-qPCR was used to measure expression of bone metabolism and inflammation-related genes,and western blot was used to measure bone metabolism and NF-a:B protein expression levels.Collagen-induced arthritis(CIA)rat model was used for pharmacodynamics study.Arthritis indexes were measured in the ankle and knee,histological staining and Micro-computed tomography were performed on the ankle joints.Also,inflammatory factor gene expression and the levels of NF-/cB-related proteins were detected as in vitro.AU effectively inhibited HFLS-RA cell migration and invasion,promoted apoptosis,and inhibited RAW264.7 cell differentiation into osteoclasts,as well as inhibited NF-/cB-p65 activity in MC3T3-E1 cells.Notably,AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors,effectively inhibited the expression of p-lKKafi,p-lA:Ba,and p-p65 proteins.In vivo,AU relieved joint inflammation,reduced related inflammatory factors,and inhibited NF-/cB signaling.It could be used to treat RA-related synovial inflammation and bone destruction through the NF-/cB pathway.展开更多
文摘Articular cartilage is a connective tissue consisting of a specialized extracellular matrix （ECM） that dominates the bulk of its wet and dry weight. Type Ⅱ collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type Ⅳ, Ⅵ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢ, and ⅩⅣ, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.
文摘用Ⅱ型胶原免疫注射 DBA/1J 小鼠,3周后用同样方法再注射,4周开始分别投与通痹灵和消炎痛。在投药12周内,观察各组四肢关节炎发病程度,16周后小鼠骨关节作 X 线片和病理组织切片,Ⅱ型胶原抗体价测定用酶结合免疫法,并检查各组血液常规、肝肾功能等。结果表明通痹灵组与阳性组和消炎痛组相比较,该药对胶原关节炎发病,血中Ⅱ型胶原抗体价和白细胞的增加,四肢关节骨破坏等病变均有显著抑制。血液常规和肝肾功能等检查均未见异常。提示本药不仅具有抗炎和免疫调节作用,而且副作用比较少。
文摘The therapeutic actions of Qing Luo Yin (QLY清络饮) with heat property and Wen Luo Yin (WLY温络饮) with cold property on pain, swelling of the ankle, arthritis index and ultrastructures of synoviocytes were compared in rats of type II collagen-induced arthritis (CIA), with tripterygium glycosidorum (TG) used as control. The results indicated that both QLY and WLY could reduce pain, swelling of the ankle and the arthritis index of CIA, and QLY had better effects in reducing the swelling of the ankle and controlling the secondary pathological lesions as compared with WLY. Investigation on the ultrastructures of synoviocytes indicated that both QLY and WLY could reduce the number of Golgi apparatus, rough surface endoplasmic reticulum, dense bodies, matrix filaments and vacuoles so as to suppress the excessive secretion of synoviocytes in rats of CIA.
基金sponsored by National Natural Science Foundation(No.81822050,81920108032,81904227)Shanghai“Science and Technology Innovation Action Plan”Medical Innovation Research Project(No.21Y11921400)+4 种基金the Program for Innovative Research Team of Ministry of Science and Technology of China(No.2015RA4002)“Innovation Team”Development Projects(No.IRT1270)Innovative Team Project of Scientific Research Project of Traditional Chinese Medicine of Shanghai Municipal Health Commission(No.2022CX001)Shanghai TCM Medical Center of Chronic Disease(No.2022ZZ01009)Jing'an District Health Research Project of Shanghai(No.2022MS03).
文摘Objective: Rheumatoid arthritis(RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction(HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis(CIA) mouse model.Methods: DBA/1J female mice were used to establish the collagen-induced arthritis(CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay(ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors m RNA and protein levels after HGWD intervention in RAW264.7 cells.Results: HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints,reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function.HGWD decreased the expression of m RNA for inflammatory factors and the protein expression levels of p-NF-ΚB and IL-17.Conclusion: These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.
基金This study was supported by the National Natural Science Foundation of China(No.81270949).
文摘Summary:Huai Qi Huang(HQH)exerts great effects in clinic,such as anti-inflammation,immune-regulation,anti-cancer,and so on.However,the mechanism by which HQH protects juvenile idiopathic arthritis(JIA)is obscure.Thus,we explored deeply the protective mechanisms in juvenile collagen-induced arthritis(CIA)rat model.Pyroptosis is Gasdermin D(GSDMD)-dependent programmed cell death,involved in many diseases,such as sepsis.We investigated whether GSDMD-induced pyroptosis take part in mechanisms of juvenile CIA arthritis.Juvenile Wistar rats(3-4 weeks)were injected intradermally with fully emulsified bovine typeⅡcollagen and complete Freund's adjuvant to establish CIA rat models.Later,the CIA rats received oral administration of HQH(4.16 g/kg)once a day from the day 21 of modeling,with the treatment lasting for 28 days.Varieties of indicators were measured for evaluation of anti-inflammation effect of HQH,including hind paw swelling,arthritis scores,micro CT,and histopathological changes and the level of pro-inflammatory cytokines in the serum,including tumor necrosis factor alpha(TNF-α)and interleukin-18(IL-18).The expression of GSDMD and caspasein the joint synovial tissues was detected.The results demonstrated that the expression of the pyroptotic protein GSDMD and its upstream caspase-1 was significantly increased in the synovial tissues of CIA rats.The treatment of HQH ameliorated the symptoms in CIA rats,reduced levels of pro-inflammatory cytokines and hind paw swelling,down-regulated the expression of GDSMD and caspase-1.GSDMDinduced pyroptosis participated in the pathogenesis of CIA rats.The study supported that HQH can effectively improve joints inflammation of juvenile collagen-induced arthritis rats by inhibiting pyroptosis pathway in the joint synovial tissues.
基金supported by the National Natural Science Foundation of China(No.82274329,82304991)the China Postdoctoral Science Foundation(No,2023M732336)Shanghai Science and Technology Committee Sailing Program Foundation(No.23YF1442500)。
文摘Rheumatoid arthritis(RA)is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation,posing challenges in the development of effective treatments.Nuciferine,an alkaloid found in lotus leaf,has shown promising anti-inflammatory and anti-tumor effects,yet its efficacy in RA treatment remains unexplored.This study investigated the antiproliferative effects of nuciferine on the MH7A cell line,a human RA-derived fibroblast-like synoviocyte,revealing its ability to inhibit cell proliferation,promote apoptosis,induce apoptosis,and cause G1/S phase arrest.Additionally,nuciferine significantly reduced the migration and invasion capabilities of MH7A cells.The therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis(CIA)rat model,where it markedly alleviated joint swelling,synovial hyperplasia,cartilage injury,and inflammatory infiltration.Nuciferine also improved collagen-induced bone erosion,decreased pro-inflammatory cytokines and serum immunoglobulins(IgG,IgG1,IgG2a),and restored the balance between T helper(Th)17 and regulatory T cells in the spleen of CIA rats.These results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.
基金National Natural Science Foundation of China:81774383,81904274supported by"Nursing Advantageous Discipline Construction Project in Jiangsu Universities"of Nanjing University of Chinese medicine:2019YSHL008,2019YSHL021。
文摘Objective:To demonstrate the rheumatoid arthritis(RA)mechanisms by determining the biochemical changes.To investigate the therapeutic mechanism of moxibustion in RA-model rats using a gas chromatography-mass spectrometry(GC-MS)metabolomics approach.Methods:A total of 24 rats were divided into three groups as follows:normal control group,model group and moxibustion group.Rats in model group and moxibustion group were set up collagen-induced arthritis(CIA)model.Rats in moxibustion group were treated by moxibustion.After 3 weeks of intervention,right ankle joint,serum and articular synovium samples were collected.Right ankle joint samples were used for histopathological evaluation between 3 groups to get the pathological changes of tissues and cells.Serum and articular synovium samples were used to analyze the changed metabolites of moxibustion on RA rats by the GC-MS based metabolomics.Results:Treatment of moxibustion not only significantly increased the weight of CIA rats,reduced the swelling of hind paw,arthritic scores,IL-1β,TNF-αbut also improved histopathological evaluation in right ankle joint samples.Sixteen significantly altered metabolites were found in RA rats as potential biomarkers of arthritis.Thirteen metabolites,significantly adjusted by moxibustion to help relieve arthritis,were selected out as biomarkers of antiarthritic mechanism of moxibustion,which were mainly involved in phenylalanine,tyrosine and tryptophan biosynthesis,glycine,serine and threonine metabolism,phenylalanine metabolism,alanine,aspartate and glutamate metabolism,glyoxylate and dicarboxylate metabolism and aminoacyl-tRNA biosynthesis.Conclusions:We have indicated moxibustion treatment is able to resist inflammation in CIA rats effectively.Using GC-MS metabolomics technique,we detect novel metabolites in the moxibustion antiarthritic process,which may aid in advanced understanding of arthritis and therapeutic mechanism of moxibustion.
基金This work was supported by the Natural Science Foundation of China(No.81773922)Shanghai Natural Science Foundation(No.19ZR1452000).
文摘Rheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease.It is known that aucubin(AU)exerts anti-inflammatory activity,but its effects and mechanisms in RA are unclear.This study investigated the anti-inflammatory effects and mechanisms of AU in vivo and in vitro.Human fibroblast-like synoviocyte cells from patients with RA(HFLS-RA),RAW264.7 cells,and MC3T3-E1 cells were used to evaluate the effects of AU on migration,invasion,apoptosis,osteoclast differentiation and production.Immunofluorescence was used to observe nuclear translocation of nuclear factor(NF)-/cB,the double luciferase reporter gene method was used to observe NF-/cB-p65 activity in AU-treated MC3T3-E1 cells.RT-qPCR was used to measure expression of bone metabolism and inflammation-related genes,and western blot was used to measure bone metabolism and NF-a:B protein expression levels.Collagen-induced arthritis(CIA)rat model was used for pharmacodynamics study.Arthritis indexes were measured in the ankle and knee,histological staining and Micro-computed tomography were performed on the ankle joints.Also,inflammatory factor gene expression and the levels of NF-/cB-related proteins were detected as in vitro.AU effectively inhibited HFLS-RA cell migration and invasion,promoted apoptosis,and inhibited RAW264.7 cell differentiation into osteoclasts,as well as inhibited NF-/cB-p65 activity in MC3T3-E1 cells.Notably,AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors,effectively inhibited the expression of p-lKKafi,p-lA:Ba,and p-p65 proteins.In vivo,AU relieved joint inflammation,reduced related inflammatory factors,and inhibited NF-/cB signaling.It could be used to treat RA-related synovial inflammation and bone destruction through the NF-/cB pathway.
