PURPOSE: To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis (PTOA) treated with 4-octyl itaconate (4-OI) and evaluate the therapeutic effects of 4-OI. METHODS: In the phenotypic validation experiment, the mice were randomly divided into 3 groups: wild-type (WT) group, sham group, and destabilization of the medial meniscus (DMM) group. Through MRI, micro-CT, and histological analysis, it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis. At 12 weeks post-DMM surgery, synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis. In the 4-OI treatment experiment, mice were randomly divided into the sham group, DMM group, DMM + 4-OI (50 mg/kg) group, and DMM + 4-OI (100 mg/kg) group. Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery. After 12 weeks of surgery, the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI, micro-CT, histological analysis, and quantitative real-time polymerase chain reaction. Finally, we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation. Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test. Difference was considered statistically significant at p < 0.05. RESULTS: The DMM surgery effectively induced a PTOA mouse model, which displayed significant symptoms of synovitis. These symptoms included a notable increase in both the number of calcified tissues and osteophytes (p < 0.001), an enlargement of the calcified meniscus and synovial tissue volume (p < 0.001), and thickening of the synovial lining layer attributable to M1 macrophage accumulation (p = 0.035). Additionally, we observed elevated histological scores for synovitis (p < 0.001). Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice (p < 0.001) and reduced fibrosis in the synovial stroma (p = 0.004). Furthermore, it reduced the histological scores of knee synovitis in PTOA mice (p = 0.006) and improved the inflammatory microenvironment associated with synovitis. Consequently, this treatment alleviated pain in PTOA mice (p < 0.001) and reduced spontaneous activity (p = 0.003). Bioinformatics and network pharmacology analyses indicated that 4-OI may exert its therapeutic effects by inhibiting the differentiation of synovial Th17 cells. Specifically, compared to the lipopolysaccharide stimulation group, 4-OI reduced the levels of positive regulatory factors of Th17 cell differentiation (IL-1: p < 0.001, IL-6: p < 0.001), key effector molecules (IL-17A: p < 0.001, IL-17F: p = 0.004), and downstream effector molecules in the IL-17 signaling pathway (CCL2: p < 0.001, MMP13: p < 0.001). CONCLUSION 4-OI is effective in inhibiting synovitis in PTOA, thereby alleviating the associated painful symptoms.
Animals ; Synovitis/etiology* ; Mice ; Osteoarthritis/etiology* ; Disease Models, Animal ; Male ; Succinates/pharmacology* ; Mice, Inbred C57BL ; X-Ray Microtomography

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is a rare seronegative synovial inflammatory disease in which fever is a rare symptom.There are few case reports of RS3PE syndrome with fever as the first clinical manifestation in China.In this paper,we report a case of RS3PE syndrome with fever as the first symptom and diagnosed by systematic fever investigation.
Humans ; Edema/etiology* ; Fever/etiology* ; Syndrome ; Synovitis/drug therapy*

Remitting seronegative symmetrical synovitis with pitting edema(RS3PE),the inflammatory arthritis attacking mainly elderly males,is characterized by symmetrical synovitis with pitting edema of the dorsum of hands and feet and the absence of rheumatoid factor.RS3PE commonly accompanies malignant tumor,infections and other diseases.Here we report a case of RS3PE associated with lung malignancy and review other six cases to summarize the clinical features,treatment and prognosis.
Aged ; Edema/etiology* ; Humans ; Lung Neoplasms/complications* ; Male ; Syndrome ; Synovitis/drug therapy*

OBJECTIVEBlau syndrome (BS), an autosomal dominant inherited autoinflammatory disease, is caused by NOD2 mutations. This study aimed to analyze NOD2 gene of suspected BS patients to make definite diagnosis, find NOD2 mutation types and clinical features of Chinese BS cases, and find some clinical indications to identify BS by comparing BS and non-BS cases.

METHODEighteen suspected BS children (7 boys and 11 girls, age of first visit was from 1 y 8 m to 9 y 6 m) who visited Peking Union Medical College Hospital from 2006 to 2014 and their parents's DNA were extracted from 4 ml blood specimens. PCR was performed for exon 4 of NOD2 and PCR products were purified by 2% gel electrophoresis and sequenced directly. Role of novel missense mutations in pathogenicity was analyzed by SIFT and sequencing NOD 2 of fifty normal controls. Clinical data of BS children diagnosed by NOD2 analysis were summarized and compared with the data of non-BS group.

RESULT(1) Twelve of eighteen suspected BS children were diagnosed as BS by NOD2 analysis, and the remaining 6 were excluded. Seven missense mutations were detected, 4 were reported before: c.1000C>T, p. Arg 334Trp; c.1001G>A, p. Arg334Gln; c.1538T>C, p. Met513Thr; c.1759C>T, p. Arg587Cys. Three novel mutations were found: c. 1147 G>C, p.Glu383Gln; c.1471A>T, p. Met491Leu; c.2006A>G, p.His669Arg. (2) Chronic symmetric arthritis and multi-joints periarticular hydatoncus, which were painless with fluctuation, were found in all 12 BS children with NOD2 mutations. Skin rash, chronic symmetric arthritis, and recurrent uveitis were identified in 7 patients. Three patients had no skin rash, while 1 had no uveitis, 1 only had symmetric arthritis and multi-joints periarticular hydatoncus. Four children inherited the disease from father. (3) Compared with other 6 non-BS children, BS children had such different clinical characteristic (P < 0.05): All the BS cases had multiple periarticular hydatoncus, which always had no persistent fever, most had no elevated CRP, while non-BS group always had no hydatoncus, most had persistent fever, all had elevated CRP.

CONCLUSIONThe 12 BS children were diagnosed by NOD2 analysis; 7 missense mutations were detected, 3 were novel mutations, adding new findings to human NOD2 mutations. Although classic BS was characterized by skin rash, arthritis, and eye involvement, some presented with less than 3 of the classic features. Chronic symmetric arthritis and multi-joints periarticular hydatoncus were the most comment fetures. Comparing with non-BS group, all BS cases had multi hydatoncus surrounding multi-joints, always had no persistent fever, most had no elevated CRP. Those features may distinguish BS in clinical settings.

Arthritis ; etiology ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Child ; Child, Preschool ; Cranial Nerve Diseases ; complications ; genetics ; Exanthema ; etiology ; Exons ; genetics ; Female ; Humans ; Infant ; Male ; Mutation ; genetics ; Mutation, Missense ; Nod2 Signaling Adaptor Protein ; genetics ; Synovitis ; complications ; genetics ; Uveitis ; complications ; etiology ; genetics

BACKGROUNDThere are few reports of a biological role for glycosyltransferases in the infiltration of osteoarthritic synovitis. The aim of this research was to investigate the expression and cellular location of β-1,4-galactosyltransferase I (β-1,4-GalT-I) in a surgically-induced rat model of knee osteoarthritis (OA), and explore the role of β-1,4-GalT-I in the pathogenesis of OA.

METHODSMale Sprague-Dawley rats were randomly divided into three groups: OA group, sham group and normal group. The model of OA was established in the right knees of rats by anterior cruciate ligament transaction (ACLT) with partial medial meniscectomy. Fibroblast-like synoviocytes (FLSs) obtained from normal rat synovial tissue were cultured. The expression of β-1,4-GalT-I mRNA in the synovial tissue, articular cartilage and FLSs treated with tumor necrosis factor-α (TNF-α) were assayed by real-time PCR. Western-blotting and immunohistochemisty were used to observe the expression of β-1,4-GalT-I at the protein level. Double immunofluorescent staining was used to define the location of the β-1,4-GalT-I with macrophage-like synoviocytes, FLSs, neutrophils, and TNF-α in the OA synovium. The alteration of TNF-α in FLSs which were treated with lipopolysaccharide (LPS) and β-1,4-GalT-I-Ab were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSThe mRNA and protein expression of β-1,4-GalT-I increased in synovial tissue of the OA group compared with the normal and sham groups at two and four weeks after the surgery, however, no significant difference appeared in the articular cartilage. Immunohistochemistry also indicated that the β-1,4-GalT-I expression in OA synovium at four weeks after surgery increased sharply compared with the control group. β-1,4-GalT-I co-localized with macrophage-like synoviocytes, FLSs, neutrophils and TNF-α in rat OA synovitis. Moreover, in vitro β-1,4-GalT-I mRNA in FLSs was affected in a dose- and time-dependent manner in response to TNF-α stimulation. ELISA revealed that the expression of TNF-α was attenuated in FLSs in vitro when treated with anti β-1,4-GalT-I antibody.

CONCLUSIONβ-1,4-GalT-I may play an important role in the inflammation process of rat OA synovial tissue which would provide the foundation for further researching into the concrete mechanism of β-1,4-GalT-I in OA synovitis.

Animals ; Blotting, Western ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Galactosyltransferases ; genetics ; metabolism ; Immunohistochemistry ; Knee Joint ; enzymology ; pathology ; surgery ; Male ; Osteoarthritis, Knee ; enzymology ; genetics ; pathology ; Polymerase Chain Reaction ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane ; enzymology ; Synovitis ; enzymology ; etiology

OBJECTIVETo study the effectiveness of radiation synovectomy with (188)Re-sulfide.

METHODSTwenty rabbit models of joint synovitis were injected intra-articularly with different doses of (188)Re-sulfide from 7.4 to 37.0 MBq. By pathological examination, the effects of (188)Re-sulfide on synovium and cartilage were evaluated. Clinically, 10 joints of 7 cases of hemophilic arthritis with (188)Re-sulfide radiation synovectomy were performed. MRI was taken before and after the synovectomy to evaluate the treatment effects.

RESULTSIn rabbit models, when (188)Re-sulfide dose larger than 14.8 MBq, the radiation effect on synovitis was remarkable, including thinning the thickened synovium and reducing the inflammatory cells. When radio-activity dose increased to 37.0 MBq, pathological damage was noted in cartilage. Clinical trial demonstrated that radiation synovectomy by (188)Re-sulfide could reduce the frequencies of intra-articular hemorrhage. MRI showed that edema and villi reduced.

CONCLUSIONSRadiation synovectomy using (188)Re-sulfide is effective on synovitis in hemophilic arthritis.

Animals ; Chlorides ; therapeutic use ; Disease Models, Animal ; Follow-Up Studies ; Hemophilia A ; complications ; Humans ; Injections, Intra-Articular ; Rabbits ; Rhenium ; therapeutic use ; Ruthenium Radioisotopes ; therapeutic use ; Sulfides ; Synovial Membrane ; radiation effects ; Synovitis ; etiology ; pathology ; radiotherapy