Expression of AIM2 in Rheumatoid Arthritis and Its Role on Fibroblast-Like Synoviocytes.

OBJECTIVES: To determine differences in AIM2 inflammasome expression levels between rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate the role of AIM2 in RA fibroblast-like synoviocytes (RA-FLS). METHODS: Serum AIM2 levels among health controls (HC, n = 20), OA (n = 25), and RA (n =49) patients were compared via ELISA. The different expression levels of AIM2, ASC, caspase-1, and IL-1ß between RA and OA synovium were semiquantified by qRT-PCR and immunohistochemical (IHC) staining. IHC staining was recorded by H scores, and its correlation with the ESR and CRP levels of RA patients was determined. SiRNA AIM2 was transferred to RA-FLS and its effects on the proliferation and migration via CCK-8 assay and Transwell test, respectively. RESULTS: In RA sera, the HC expressed higher level of AIM2 than OA and RA patients, and ASC, caspase-1, and IL-1ß expressed higher in RA patients than HC; no significant differences were observed between sera of OA and RA patients. However, in affected knee synovium, AIM2, ASC, caspase-1, and IL-1ß were expressed higher in RA than that of OA. Moreover, the H scores of AIM2, ASC, and IL-1ß were positively correlated with the ESR and CRP levels in RA patients. The proliferation of FLS was significantly inhibited after transferring with AIM2 siRNA to FLS. There were no differences in apoptosis and migration assay between the si-AIM2 group and the control group. CONCLUSION: AIM2 inflammasome pathway involves in the pathogenesis of RA. si-AIM2 inhibits the proliferation of RA-FLS, which may be a promising therapeutic strategy for the treatment of RA.

[What happened in the acupoint area of mouse after blood injection?]

OBJECTIVE: Autologous blood acupoint injection has practiced for treatment of various diseases, but its therapeutic mechanism remains unknown. This study aimed to explore the histological changes in the acupoint area after blood injection. METHODS: Blood samples (0.1 mL) collected from donator mice was injected in the recipient mice at the acupoint of left Zusanli (ST- 36). At 0, 6, 12, 24, 48, 72 and 96 h after the injection (3 mice at each time point), peripheral blood and muscular tissue were collected from the injection site for blood cell classification and histological study with HE staining. RESULTS: White blood cells and lymphocytes tended to increase but platelets tended to decrease at the acupoint after blood injection, but these changes were not statistically significant. Within 24 h after blood injection, acute inflammation occurred at the acupoint, and the injected blood components were infiltrated by neutrophils; a small number of monocytes were observed at the injection site, where red blood cells gradually disappeared. From 24 to 96 h, the injected area showed chronic inflammation with infiltration by mononuclear cells, macrophages, and lymphocytes, and the number of fibroblasts increased and neutrophils decreased gradually over time; the local muscle fibers were destroyed, and proliferation of fibrous tissue could be seen. CONCLUSIONS: Blood injection at the acupoints can mimic the process of hematoma absorption in the muscular tissue, and local inflammation is initiated to engulf and clear the blood components, which may be the basis for the therapeutic effects induced by acupoint stimulation.

What happened in the acupoint area of mouse after blood injection? / 南方医科大学学报

OBJECTIVE@#Autologous blood acupoint injection has practiced for treatment of various diseases, but its therapeutic mechanism remains unknown. This study aimed to explore the histological changes in the acupoint area after blood injection.@*METHODS@#Blood samples (0.1 mL) collected from donator mice was injected in the recipient mice at the acupoint of left Zusanli (ST- 36). At 0, 6, 12, 24, 48, 72 and 96 h after the injection (3 mice at each time point), peripheral blood and muscular tissue were collected from the injection site for blood cell classification and histological study with HE staining.@*RESULTS@#White blood cells and lymphocytes tended to increase but platelets tended to decrease at the acupoint after blood injection, but these changes were not statistically significant. Within 24 h after blood injection, acute inflammation occurred at the acupoint, and the injected blood components were infiltrated by neutrophils; a small number of monocytes were observed at the injection site, where red blood cells gradually disappeared. From 24 to 96 h, the injected area showed chronic inflammation with infiltration by mononuclear cells, macrophages, and lymphocytes, and the number of fibroblasts increased and neutrophils decreased gradually over time; the local muscle fibers were destroyed, and proliferation of fibrous tissue could be seen.@*CONCLUSIONS@#Blood injection at the acupoints can mimic the process of hematoma absorption in the muscular tissue, and local inflammation is initiated to engulf and clear the blood components, which may be the basis for the therapeutic effects induced by acupoint stimulation.

Differential expression analysis of absent in melanoma 2-inflammasome pathway associated protein in rheumatoid arthritis and osteoarthritis synovium / 中华风湿病学杂志

Objective:To compare the expression levels of absent in melanoma 2 (AIM2) inflammasome pathways in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial specimens.Methods:Synovial tissue samples were collected from 41 RA and 26 OA patients, respectively. Horseradish peroxidase immunohi stochemical staining was used to detect AIM2 inflammasome pathway-related proteins, including AIM2, apoptosis-associated speck-like protein containing a CARD(ASC), caspase-1, and interleukin-1 (IL-1β). A semi-quantitative score (H-score) was performed according to the degree of positiveness. Correlation analysis between H-score results and clinical indicators of erythrocyte sedimentation tate (ESR) and C-reactive protein (CRP) were performed. The H score between RA and OA was analyzed by t test and Spearman correlation analysis were utilized for correlation analysis between H score and ESR and CRP.Results:The H scores of AIM2 protein in RA synovial tissues was (132±7) and (54±8) in OA synovial tissues ( t=7.42, P<0.01). The H scores of ASC protein in RA synovial tissues was (107±9) and (74±6) in OA synovial tissues ( t=2.36, P<0.05). The H scores of caspase-1 protein in RA synovial tissues was (99±5) and (74±10) in OA synovial tissues ( t=2.15, P<0.05). The H scores of IL-1β protein in RA synovial tissues was (118±11) and (76±7) in OA synovial tissues ( t=3.30, P<0.05) . In the correlation analysis, AIM2 was positively correlated with ESR [ r=0.74, P<0.01, 95% CI(0.38, 0.9)], and ASC was positively correlated with ESR [ r=0.5, P<0.05, 95% CI(0.16, 0.74)], IL-1β was positively correlated with ESR [ r=0.62, P<0.05, 95% CI (0.31, 0.81)], and the difference was statistically significant ( P<0.05). At the same time, AIM2 was positively correlated with CRP [ r=0.65, P<0.05, 95% CI(0.25, 0.86)]; ACS was positively correlated with CRP [ r=0.42, P<0.05, 95% CI(0.05, 0.69)]. IL-1β was positively correlated with C-reactive Protein [ r=0.41, P<0.05, 95% CI(0.05, 0.67)] and positively correlated with C-reactive protein, and the difference was statistically significant ( P<0.05). Conclusion::The expression of AIM2 inflammasome pathway-related proteins in RA synovium, including AIM2, ASC, caspase-1, and IL-1β, is higher than that of OA and are positively correlated with disease activity. Activation of AIM2 inflammasome pathway may be associated with the pathogenesis of RA disease activity.

Pannus does not occur only in rheumatoid arthritis: a pathological observation of pannus of knee osteoarthritis / 南方医科大学学报

OBJECTIVE@#To compare the histopathological features of the synovium between rheumatoid arthritis (RA) and osteoarthritis (OA).@*METHODS@#We retrospectively analyzed the synovial specimens obtained after synovial surgery in 72 cases of RA and 24 cases of OA. Two independent pathologists reviewed the sections of the synovial tissues with HE staining, quantitatively scored the degree of fibroblast-like synoviocyte (FLS) hyperplasia, vascular hyperplasia, fibroplasia, and lymphocyte infiltration, and examined the presence plasma cell infiltration. The pathological morphology of the synovial tissues was evaluated in relation with the clinical data of the patients.@*RESULTS@#Pannus formation was also detected in the synovium of OA patients, which showed a lesser degree of OA-FLS hyperplasia, fibrosis and lymphocyte infiltration and a significantly lower rate of plasma cell infiltration compared with the pannus in RA patients. Vascular proliferation was also milder in the pannus of OA patients than in RA pannus, but the difference was not statistically significant. In OA patients, the pannus could be observed under a microscope and was difficult to distinguish from that in RA patients.@*CONCLUSIONS@#Pannus formation occurs also in the synovium of OA patients but with milder FLS hyperplasia, fibrosis and lymphocyte infiltration and a lower rate of plasma cell infiltration compared with the pannus in RA patients. These differences in the pannus between OA and RA can be of potential value in the diagnosis and treatment of the patients.