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The protective effect of sodium hyaluronate on the cartilage of rabbit osteoarthritis and its effects on PPAR-gamma mRNA expression

Jianlin ZHOU ; Shiqing LIU ; Bo QIU ; Hao PENG ; Jianghua MING

Chinese Journal of Rheumatology.2009;13(2):-. doi:10.3760/cma.j.issn.1007-7480.2009.02.014

Objective To observe the protective effect of sodium hyaluronate (Na-HA),and its effects on mRNA expression of peroxisome proliferators-activated receptor gamma (PPAR-γ) in cartilage of rabbit osteoarthritis (OA) model.Methods Forty eight white rabbits were divided into A,B,C groups randomly.Group A were normal controls,groups B and C were underwent unilateral anterior cruciate ligament transection (ACLT).The rabbits in group B were injected normal saline after ACLT;Group C rabbits received intra-articular 1% sodium hyaluronate (HA) injections 5 weeks after surgery,0.3 ml once a week.At week 11 after the surgery,all rabbits were sacrificed.The cartilage changes on the medial femoral condyles were graded.Cartilage sections were stained with safranin-O and HE,mRNA expression of PPAR-γ was detected by real time polymerase chain reaction (Real Time-PCR).Results Cartilage degeneration in group B was significantly more severe than in groups A and C.The grey value of Safranin-O of B group were higher than groups A and C.Expression of PPAR-γ mRNA in group B was higher than that in groups A and C.Conclusion NaHA has a protective effect on articular cartilage degeneration,and the inhibitory effect on PPAR-γ mRNA expression may be one of the therapeutic mechanism of Na-HA.

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Clinicopathulogic correlation in lupus nephritis:281 eases analysis

Chaosheng CHEN ; Feifei XU ; Yinqiu LV ; Chaoxing HUANG ; Xiaochun ZHU ; Yulan XU

Chinese Journal of Rheumatology.2008;12(8):554-556,插二.

Objective To investigate the clinical manifestations,laboratory findings and renal patho logic changes,as well as their relationships in patients with lupus nephritis (LN).Methods According to the latest classification criteria of lupus nephritis,the clinical manifestations,laboratory findings and renal patho logic changes and their relationships of 281 cases of biopsy proven LN were retrospectively analyzed.Results Totally 281 cases of LN patients were enrolled in total.The ratio of male to female was 1∶9.7.Proteinuria ac companied with hematuria (35.2%) and nephrotie syndrome (33.8%) were the main clinical manifestations. The most common renal pathological change was type Ⅳ LN (35.9%) and type Ⅲ,Ⅳ and Ⅴ accounting for 89.0% totally.The main pathologic changes of nephrotic syndrome were type Ⅳ and Ⅴ,while those who ac companied with renal dysfunction were mainly type Ⅵ and Ⅳ.Most simple hematuria cases showed mild renal injury.However,type Ⅳ and Ⅴ accounted for 40.4% in the 47 cases of LN whose 24 hours urine protein＜ 1.0 g and with normal renal function.Most severe proteinuria was found in Type Ⅴ and higher serum creatinine and anti-dsDNA antibody level were found in type Ⅵ and Ⅳ.The lowest lever of serum complement 3 (C3) was found in type Ⅳ.The amount of 24 hours urine protein showed negative correlation with semm C3 but positive correlation with serum creatinine.Serum C3 demonstrated negative relationship with serum creatinine and anti-dsDNA antibody,while serum creatinine was positively related to anti-dsDNA antibody level. Conclusion The major renal pathological lesions of LN are type Ⅲ,Ⅳ and Ⅴ.There are associations be tween clinical and pathological changes,but axe not always consistent.Proteinuria,low serum C3 and high an ti-dsDNA antibody level may provide clue to severe and active LN.Renal biopsy is important in the diagnosis and progression evaluation of LN.

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The distribution and effect of allogenic mesenchymal stem cells on joints of collagen induced arthritis rats

Lihui MA ; Zhenhua QIAO ; Xiaofeng LI

Chinese Journal of Rheumatology.2011;15(6):376-380,后插1. doi:10.3760/cma.j.issn.1007-7480.2011.06.005

Objective To study the distribution of allogenic bone marrow-derived mesenchymal stem cells (BM-MSCs) on joints of collagen-induced arthritis (CIA) rats and to investigate their repair effects on joint damages. Methods Five Wistar rats were used for extraction of mesenchymal stem cells and 30 adult female Wistar rats were divided into 3 groups: the CIA rats group A (n=10), CIA rats group B (n=10) and normal rats control group C (n=10). BM-MSCs of Wistar rats were isolated, cultured in vitro routinely and the fourth passages was taken for identification of specific surface antigens by flow cytometry, then the cells were labeled with 5-bromodeoxyuridine (5-BrdU) in vitro. The models of CIA rats were established. 5-BrdU labeled BM-MSCs (1.0×107 cells/kg) were imfused from through tail vein to CIA rats group A and control group C. During the first 4 weeks after BM-MSCs transplantation, changes of general condition and left hind paw swelling were examined. At the fourth week, immunohistochemical examination of 5 -BrdU and osteoprotegerin (OPG) were performed to investigate BM-MSCs aggregation around the knee joints. The contribution of BM -MSCs to repairing of joint damages was identified. Comparisons between groups were performed by t-test. Results After BM-MSCs transplantation, left hindpaw swelling of group A were relieved compared with group B (P＜0.05) and the mobility of the joints was significantly improved. At the fourth week, much more implanted cells (5-BrdU positive cells.) were detected in the damaged knee joints than those in normal knee joints. The average grey scale values on synovium of knee joints in the CIA group A (85±9) was significantly lower than that of the normal group C (110±6, P＜0.05). At the same time, OPG expression was increased in damaged knee joints. The average grey scale values on synovium of knee joints in CIA group A (54±4) was significantly lower than that of the CIA group B (77±6, P＜0.05). Conclusion The transplanted allogeneic bone marrow mesenchy-mal stem cells can migrate to sites of damaged tissue in arthritis. They can prevent tissue damage and repair the damaged joints tissue by increasing OPG expression. This study has provided some evidence for developing effective therapy for rheumatoid arthritis.

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The role of neuro-associated autoantibodies in neuropsychiatric systemic lupus erythematosus

Xiaofeng SHAO ; Yongzhe LI ; Yin SU ; Wei ZHAO ; Wei CUI ; Zhanguo LI

Chinese Journal of Rheumatology.2008;12(8):519-523,插一.

Objective To evaluate the specificities and sensitivities of neuron-assoeiated(Neu-A) autoantibodies in the diagnosis of neuropsychiatric systemic lupus erythematosus(NPSLE)and explore its role in the pathogenesis of NPSLE.Methods The ncuro-associated autoantibodies including anti-neuroblastoma cell,anti-neuroglioma cell,and anti-brain,anti-spinal antibodies were tested using neuroblastoma cell line SK-N-SH.ueuroglioma cell line U251 or cerebrum and spinal meduHa of mice C57BL/10 as substrates respec tively,Serums of 121 SLE patients fincluding 36 NPSLE patients and 85 systemic lupus erythematosus (SLE)patients without CNS involvement),34 rheumatoid arthritis(RA)patients and 34 healthy controls were tested by indirect immunofluorescence(IIF)assay.Cerebrospinal fluid of 24 NPSLE patients and 22 CNS dis eases controls were also tested.Results The positive rates of anti-neuroblastoma cell antibodies,anti-brain and anti-spinal antibodies in serums of SLE patients were 17.4%,25.6%and 29.8%,respectively.Only 2.9%, 5.9%,0 in 34 RA patients and 0,2.9%,0 in health controls were positive(P＜0.05 or P＜0.01).The specificity of the three antibodies in SLE was 98.5%.95.6%and 100%respectively.Anti-neuroblastoma cell antibodies, anti-brain and anti-spinal antibodies were closely associated with SLEDAI score.The NPSLE patients with positive anti-neuroblastoma cell antibodies,anti-brain or anti-spinal antibodies had frequent seizure atlacks, headache,acute confusion state and mood disorders.There was a higher prevalence of anti-neuroblastoma cell.anti-brain and anti-spinal antibodies in NPSLE than those in SLE patients.29.2%anti-brain and anti- spinal antibodies were detected in the eerebrospinal fluid of NPSLE patients.which were significantly higher than those of disease control group(P＜0.05 or P＜0.01).The specificities of these two antibodies jn NPSLE were 100%and 95.5%respectively.Conclusion Anti-neumhlastoma cell antibody.anti-brain and anti spinal antibodies are valuable markers for the diagnosis of SLE.They are closely associated with the disease activity of SLE and neuropsychiatric symptoms.Anti-spinal antibody may be a sensitive and specific marker for the diagnosis of NPSLE while anti-brain and anti-spinal antibodies in the cerebrospinal fluid are more specifie for the diagnosis of NPSLE.

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Significance and distribution of lymphopenia and anti-lymphocyte antibody in systemic lupus erythematosus

Chun LI ; Xiaoyan LU ; Jing LI ; Jing HE ; Hua YE ; Rong MU ; Zhanguo LI

Chinese Journal of Rheumatology.2009;13(5):316-319,前插2. doi:10.3760/cma.j.issn.1007-7480.2009.05.009

Objective To investigate the significance and distribution of lymphopenia and antilymphocyte antibody(ALA) in systemic lupus erythematosus (SLE) and to explore the role of ALA in lympho penia.Methods One hundred and ten in-patients who were admitted during February 2003 to February 2008 were retrospectively reviewed.Indirect immunofluorescence test was used to detect ALA.Results ① Lymphopenia (＜1.5×109/L) was observed in 68.2% patients.Lymphopenia was associated with skin rashes,serositis,renal involvement,NPSLE,leucopenia,ANA,ds-DNA antibody,ESR and IgG levels.The lymphocyte count and SLEDAI scores was more closely correlated than total white blood cell counts.②ALA was positive in 51/110 (46.4%) patients.ALA was associated with renal involvement,NPSLE,WBC count,C3 level decrease,ANA,dsDNA antibody and SLEDAI scores.Conclusion Lymphopenia is significantly associated with SLEDAI scores.ALA is possibly one cause of lymphcytopenia.In addition,ALA is also a parameter for disease activity,and is associated with organ involvement and outcomes.

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Interleukin-17 expression in salivary glands and peripheral blood of patients with primary Sjogren's syndrome

Ximei WANG ; Xiaomei LI ; Xiangpei LI ; Xinoqiu WANG ; Yan MA ; Wei WANG ; Yiping WANG

Chinese Journal of Rheumatology.2009;13(5):292-295,前插1. doi:10.3760/cma.j.issn.1007-7480.2009.05.002

Objective To investigate the expression of interleukin-17 in the salivary gland and peripheral blood of patients with primary Sjogren's syndrome (pSS).Methods Biopsy specimens of labial glands were collected from 30 patients and 5 controls.Immunohistochemistry examination was conducted to detect IL-17 expression cells (Th-17),while CD45RO and CD20 were tested by using monoclonal antibodies.IL-17 levels were assessed by ELISA in 30 pSS patients and 20 healthy controls.Results Th-17 cell numbers in the salivary glands of pSS patients with few infiltrating lymphocytes were lower than that with massive infiltrating lymphocytes (15±5 vs 21±8,P＜0.05).However,the percentage of Th-17 positive cells over the total infiltrating lymphocytes in the salivary glands of pSS patients with few infiltrating lymph-ocytes was higher than that with massive infiltrating lymphocytes (P＜0.05).There was no expression of IL-17 in the controls.The distribution pattern of Th-17 was shown that Th-17 cells were distributed evenly in the salivary glands of pSS patients with few infiltrating lymphocytes,but only appeared in the periphery zone of massive or focal infiltration in the glands of pSS patients with massive infiltrating lymphocytes.The amount of Th-17 positive cells were associated with the disease activity which was evaluated by levels of erythrocyte sedimentation rate (r=0.557,P＜0.05).There was no significant differ-ence in IL-17 levels of peripheral blood between patients with pSS and normal controls.Conclusion The results of this study have shown that Th-17 is expressed in the salivary glands of patients with pSS,which indicates that IL-17 may play an important role in the pathogenesis of salivary gland destruction.

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Association between discoidin domain receptor 2 and cartilage damage

Yonghong HU ; Xiaojuan GUO ; Dong CHANG ; Hongwei YANG ; Peilin LIU

Chinese Journal of Rheumatology.2009;13(2):-. doi:10.3760/cma.j.issn.1007-7480.2009.02.008

Objective To detect the changes in the expression of discoidin domain receptor 2(DDR2)and matrix metalloproteinase (MMP)-13 in different stages of cartilage and synovium damage of osteoarthritis rats.The relation between DDR2 and the degree of cartilage damage was explored.Methods Modified papain knee joint injection approach was adopted to establish animal model of OA.The expression and distribution of protein of DDR2 and MMP-13 were checked in articular cartilage and synovium at different stages of OA.Results The expressions of DDR2 in articular cartilage and synovium of experimental groups were different from those of the normal group (P＜0.01).They were higher in cartilage than those in the corresponding synovium.The expressions of MMP-13 demonstrated the same characteristics with those of DDR2,r=0.93(P＜0.01).Conclusions The important role of DDR2-MMP-13 in cartilage damage has been proven in the pathogenic process of OA.The upregulated expressions of DDR2 in articular cartilage and synovium have a detrimental effect on cartilage degeneration.

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Expressions and role of bone morphogenetic protein 2 bFGF Cbfa1 in the process of pathological bone formation in ankyiosing spondylitis

Jianming LI ; Tongwei CHU ; Yue ZHOU

Chinese Journal of Rheumatology.2008;12(8):563-564,插一.

Objective To investigate the expressions and role of bone morphogenetic protein(BMP) 2,basic fibroblast growth factor(bFGF),Core-binding factor al(Cbfa1)in the process of pathological bone formation in ankylosing spondylitis.Methods The expressions of BMP-2,bFGF and Cbfa1 in the synovial tissues of AS patients'sacroiliac ioint were detected using in situ hybridization.They were compared with those of patients with hip replacement and the gray scale of cells was analyzed with image analysis.Results The positive expressions of BMP-2,bFGF and Cbfal in the synovial tissues of patients'sacroiliac joint with AS were stronger than those of the control group(P＜0.01).Conclusion BMP-2,bFGF and Cbfal are important factors in the process of pathological bone formation in patients with AS.They areclosely correlated with the process of bone formation in patients'sacroiliac ioint with AS.Reduction of the expressions of BMP-2,bFGF and Cbfa1 with AS can block the process of pathological bone formation.

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Expression of E-cadherin, β-catenin in labial salivary glands of patients with primary Sj(o)gren's syndrome

Hong ZHU ; Li WANG ; Xuemei WANG ; Rong ZHU ; Caixia ZHU ; Bo TIAN ; Yi GONG

Chinese Journal of Rheumatology.2011;15(6):394-399,后插1. doi:10.3760/cma.j.issn.1007-7480.2011.06.009

Objective To study the expression of E-cadherin( E-cad), p-catenin(β-cat) in labial salivary glands of patients with primary Sj(o)gren's syndrome (pSS) in order to explore their role in pathogenesis. Methods Biopsies of labial salivary glands were obtained from 52 patients with pSS and 30 healthy controls. The immunohistochemical staining was used to detect the expression of E-cad and β-cat. Anti-SSA and anti-SSB antibodies were measured. Semi-quantitative analysis was performed by image analysis software. Ultra-structural changes was used by electron-microscopic techniques. Results ① The area of expression, optical intensity and the accumulated optical intensity of the E-cad group [(2513±1086) μm2, 0.212±0.041, 566 ±297 ] were lower than normal controls. The expression level was reduced as the increase of lymphocyte infiltration focus. ② The area of expression, the optical density and the accumulated optical density of the β- cat group [(12 324±7883) μm2, 0.113±0.031, 566±297] was lower than those of the control group. The expression level was reduced as the increase of the lymphocyte infiltration focus. ③ The E-cad expression and the p-cat expression was positively correlated in the labial gland of patients with pSS. ④ Howev-er, there was difference in the expression of E -cad and β -cat between patients with positive SSA and negative SSA antibodies. Conclusion In salivary samples, the expression of both E-cad and p-cat in patients with pSS is lower than those of the controls. Anti-SSA/SSB antibodies are important parameters of pSS and they may be involved in the pathogenesis of pSS.

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The expressions and value of von willebrand factor and P-selection in renal tissues of lupus nephritis and their significance

Wen LU ; Zhaoxia LIU ; Hao QIAN ; Yajuan DENG

Chinese Journal of Rheumatology.2012;16(5):313-316,封3. doi:10.3760/cma.j.issn.1007-7480.2012.05.007

Objective To investigate the clinic-pathological significance of von Willebrand factor (vWF) and P-selectin expression in patients with lupus nephritis (LN).Methods Biopsy specimens from 71patients with LN whose disease course ranged from 2 months to 10 years were examined and scored according to a standardized method.SLE activity was evaluated by the SLE disease activity index (SLEDAI) and the British Isles Lupus Assessment Group index.Immunohistochemistry was used to detect the expressions of vWF and P-selectin in the renal tissue of LN patients and 10 normal controls.Of all the patients,7 had World Health Organization type Ⅱ,10 had type Ⅲ and 36 had WHO type Ⅳ,18 had type Ⅴ lupus nephritis.At the same time,the 24-h urine protein (UP) excretion level,the serum creatinine,the serum C3,C4,album level,antinuclear antibody (ANA),anti-double stranded DNA and disease activity scores of all patients were detected.The relationship of their expressions with the clinicopathological parameters of lupus nephritis was analyzed.ANOVA,Nemenyi test and Pearson's analysis were used for statistical analysis.Results Compared with the control group,the in situ expressions of vWF and P-selectin in the lupus nephritis patients were significantly higher.Among these patients,renal expressions of vWF were higher in type Ⅳ (0.30±0.10) than those with type Ⅱ and Ⅲ (0.12±0.05,0.22±0.14)(x2=9.273,x2=8.712,P＜0.05),while the expressions of P-selectin were higher in type Ⅳ and Ⅴ (0.29±0.05,0.36.±0.10)than those in type Ⅱ and Ⅲ (0.27±0.09,0.29±0.05 )(P＜0.05).Correlation analysis indicated that vWF was correlated significantly with AI and 24-h UP (r=0.403,0.332,P＜0.05 ),while P-selectin was correlated significantly with the scores of activity index (AI),24-h UP excretion rate and SLEDAI (r=0.283,0.453,0.297,P＜0.05 ).The expression of vWF was also closely related to P-selectin expressions (r=0.371,P=0.001).Conclusion These results indicate that vWF and P-selectin play a critical role in the pathogenesis of LN.The detection of these two factors will provide a valuable clinical reference for renal damage.These information provide valuable clues for making better treatment regimen plan and achieving more favorable prognosis.

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