1.4-Octyl itaconate inhibits synovitis in the mouse model of post-traumatic osteoarthritis and alleviates pain.
Yu-Zhen TANG ; Wan CHEN ; Bao-Yun XU ; Gang HE ; Xiu-Cheng FAN ; Kang-Lai TANG
Chinese Journal of Traumatology 2025;28(1):50-61
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
2.Remitting Seronegative Symmetrical Synovitis With Pitting Edema Syndrome With Fever as the First Clinical Manifestation:Report of One Case.
Tian-Chang ZHONG ; Zi-Hao FANG ; Ying-Yan WEN ; Kang-An LAI ; Jia-Chun LI
Acta Academiae Medicinae Sinicae 2024;46(6):970-973
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*
3.Clinical analysis of 49 cases of non-inflammasome related conditions.
Cai Hui ZHANG ; Ming Sheng MA ; Wei WANG ; Shan JIAN ; Lin WANG ; Ji LI ; Xiao Yan TANG ; Yu ZHANG ; Mei Ying QUAN ; Le Jia ZHANG ; Hong Mei SONG
Chinese Journal of Pediatrics 2022;60(12):1266-1270
Objective: To summarize the clinical characteristics and provide clues for early identification of non-inflammasome related conditions. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 49 children with non-inflammasome related conditions in Peking Union Medical College Hospital from January 2006 to February 2022 were retrospectively analyzed. Results: A total of 49 children, 29 of them were boys and 20 were girls. The age of onset was 0.8 (0.3, 1.6) years, the age at diagnosis was 5.7 (2.8, 8.8) years, and the time from onset to diagnosis was 3.6 (1.9, 6.3) years. Combined with genetic testing results, 49 children with non-inflammasome related conditions were found, including 34 cases (69%) of Blau syndrome, 4 cases (8%) of tumour necrosis factor receptor-associated periodic syndrome, 4 cases (8%) of haploinsufficiency of A20, 2 cases (4%) of Majeed syndrome, 2 cases (4%) of pyogenic sterile arthritis, pyoderma gangrenosum, acne syndrome and 3 cases (6%) of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome. There were 22 cases (45%) with a positive family history. The clinical manifestations included 37 cases (76%) cases with rash, 38 cases (78%) with joint involvement, 33 cases (67%) with eye involvement, 17 cases (35%) with recurrent fever. In addition, 11 cases (22%) were complicated with digestive system involvement. Thirty cases (61%) presented as elevated inflammatory indexes (erythrocyte sedimentation rate and (or) C-reactive protein), positive autoantibodies were noticed in 3 cases (6%). The patients were treated with glucocorticoid in 23 cases (47%), immunosuppressive agents in 43 cases (88%) and biologic agents in 37 cases (76%). During the follow-up of 5.8 (2.9, 8.9) years, 3 cases (6%) died. Conclusions: The symptoms of non-inflammasome related conditions include recurrent fever, rash, joint and ocular involvement with increased inflammatory indexes and negative autoantibodies. Up to now, glucocorticoids, immunosuppressants and biologic agents are the most popular medications for the non-inflammasome related conditions.
Male
;
Child
;
Female
;
Humans
;
Retrospective Studies
;
Synovitis
;
Arthritis, Infectious
;
Exanthema
;
Glucocorticoids
;
Autoantibodies
4.Construction and pathological characterization of 3 animal models of temporomandibular joint degenerative joint disease in mice.
Xin LIU ; Heng Hua JIANG ; Hui Min LI ; Ya Ping FENG ; Li Qin XU ; Hui Lin GUO ; Ying Jie LI ; Jin KE ; Xinig LONG
Chinese Journal of Stomatology 2022;57(10):1057-1064
Objective: To explore the pathological characteristics of three mice models of temporomandibular joint degenerative joint disease (TMJDJD), including osteoarthritis and osteoarthrosis, and to provide references for animal experimental study regarding the pathological mechanism of osteoarthritis and osteoarthrosis. Methods: A total of 54 8-week-old male C57BL/6 mice were selected to construct three TMJDJD animal models, including bilateral temporomandibular joint (TMJ) Freund's complete adjuvant (FCA) injection model, bilateral TMJ monosodium iodoacetate (MIA) injection model, and right TMJ discectomy model. FCA injection model (15 mice) was divided into saline injection group, FCA injection group-1 week, FCA injection group-2 week, FCA injection group-4 week and FCA injection group-6 week, 3 mice were used at each time point, with a total of 6 TMJs on both sides. MIA injection model (15 mice) was separated into saline injection group, MIA injection group-1 week, MIA injection group-2 week, MIA injection group-4 week and MIA injection group-6 week, 3 mice were used at each time point, with a total of 6 TMJs on both sides. TMJ discectomy model (24 mice) was split into control group, discectomy group-2 week group, discectomy group-4 week and discectomy group-6 week, six mice were used at each time point, with a total of six right TMJs. General pictures of the bilateral joints area of mice were collected 1 day after drug injection, and stereoscopic images of condylar tissues were collected 4 weeks after microsurgery for discectomy. Mouse TMJ tissue sections from each time point were stained with HE and toluidine blue, respectively, synovial tissues were scored for synovial inflammation, and the percentage of proteoglycan in condylar cartilage was quantitatively analyzed. Results: One day after intra-articular FCA or MIA injection, the width of bilateral TMJ were significantly increased in FCA injection groups [(24.60±0.46) mm] compared with the saline injection group [(21.63±0.52) mm] (t=4.25, P<0.013), the width of bilateral TMJ in MIA injection groups [(24.50±0.62) mm] were also significantly higher than that in saline injection group [(21.40±0.52) mm] (t=3.82, P=0.019). The synovitis scores in FCA injection groups 1, 2, 4, 6 weeks after FCA injection were significantly higher than that of the saline injection group (F=18.09, P<0.001), with the proteoglycan of condylar cartilage increased firstly and then decreased compared with the saline injection group (F=21.59, P<0.001). Condylar cartilage proteoglycan loss in different degrees were observed 1, 2, 4 and 6 weeks after MIA injection (F=13.59, P<0.001), and synovitis scores were increased at different degrees compared with saline injection group (F=14.79, P<0.001). The morphology of condylar cartilage in discectomy groups mice were severely damaged, synovial tissues showed dense connective tissue lesions at 2, 4 and 6 weeks postoperatively, condylar cartilage tissues showed a time-dependent loss of proteoglycan compared with the control group (F=40.62, P<0.001). Conclusions: Intra-articular FCA injection establishes a mouse model of TMJ osteoarthritis with severe synovial inflammation. Intra-articular MIA injection constructs a mouse model of typical TMJ osteoarthritis. Discectomy establishes a mouse TMJ osteoarthrosis model with severe condylar cartilage destruction.
Mice
;
Male
;
Animals
;
Cartilage, Articular
;
Osteoarthritis/pathology*
;
Iodoacetic Acid
;
Tolonium Chloride
;
Mice, Inbred C57BL
;
Temporomandibular Joint/pathology*
;
Disease Models, Animal
;
Proteoglycans
;
Synovitis/pathology*
;
Inflammation/pathology*
5.Diagnosis and differentiation diagnosis of primary temporomandibular joint cartilage and giant cell related tumor lesions.
Shi Lei NI ; Zhi Min LI ; Hong Chen SUN
Chinese Journal of Stomatology 2022;57(11):1097-1101
Cartilage and giant cell-related neoplastic lesions originating in the temporomandibular joint region have similar clinical, imaging and pathological manifestations, making the diagnosis of these disorders challenging to varying degrees. Diagnostic findings can influence treatment procedures and a definitive pathological diagnosis is important for the prognosis of these conditions. In this article, we discuss the pathological diagnosis and differentiation of four benign cartilage and giant cell related tumors and tumor-like lesions that occur in the temporomandibular joint, namely synovial chondromatosis, tumoral calcium pyrophosphate deposition disease, pigmented villonodular synovitis and chondroblastoma, taking into account their clinical features and histological manifestations, with a view to providing a basis for clinical management.
Humans
;
Temporomandibular Joint/pathology*
;
Chondromatosis, Synovial/pathology*
;
Synovitis, Pigmented Villonodular/pathology*
;
Giant Cells/pathology*
;
Cartilage
7.Remitting Seronegative Symmetrical Synovitis with Pitting Edema associated with Lung Malignancy:Case Report and Literature Review.
Juan HUANG ; Huan Yu MENG ; Li Jing WANG ; Bi Xiu HE ; Hong Wei XU ; Lin ZHOU
Acta Academiae Medicinae Sinicae 2021;43(1):149-152
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*
8.Progress on surgical treatment for hemophiliac arthropathy.
Shao-Ning SHEN ; Dong-Xiao WU ; Pei-Jian TONG
China Journal of Orthopaedics and Traumatology 2021;34(9):820-825
Surgical treatment is the main treatment for hemophilia arthritis, including synoviectomy, joint replacement and joint fusion. Synoviectomy is suitable for early hemophilia synovitis, and is divided into radiation, chemical, arthroscopy, and open operation. Radionuclides were recommended as the first choice due to its positive efficacy and less side effects, but exsit some problems such as scarcity of nuclides. Chemical synoviectomy is cheap and easy to operate, which is suitable for developing countriesm, while mutiple doses and pain after injection are main fault. Synoviectomy under arthroscope has a significant effect on the advanced lesion, but has a higher surgical risk. Open surgery with severe trauma and postoperative joint stiffness, is rarely performed. Joint replacement could effectively improve range of motion in advanced patients and is suitable for joints with high range of motion. Arthrodesis are effective in improving symptoms but lead to loss of range of motion and are suitable for joints with low range of motion. Operation for hemophilia arthritis has some problems, such as single operation, untimely diagnosis and treatment in early stage, and unsatisfactory curative effect in late stage. In addition, the treatment of hemophilia arthritis should focus on the early treatment, the formation of the whole process, the system of individual treatment concept.
Arthrodesis
;
Hemophilia A/complications*
;
Humans
;
Joint Diseases
;
Synovectomy
;
Synovitis
;
Treatment Outcome
9.Rheumatoid arthritis combined with pigmented villonodular synovitis: A case report and literature review.
Journal of Peking University(Health Sciences) 2020;52(6):1135-1139
We reported a case of rheumatoid arthritis (RA) combined with pigmented villonodular synovitis (PVNS) from Peking University People's Hospital. The clinical data were introduced and the related literature was reviewed. The clinical features, treatment and prognosis of the disease were summarized to improve clinicians' understanding of this rare disease and avoid misdiagnosis and delayed diagnosis. A 45-year-old female, with 15 years of RA history and unregular treatment, was admitted to the hospital with the complaint of aggravating pain and swelling in the right knee for 3 months. The puncture of the right knee was performed and there was a large amount of bloody synovial fluid that could not be explained by her RA history. Moreover, the magnetic resonance imaging (MRI) of the right knee revealed hemosiderin deposition with low-intensity signals on both T1-weighted and T2-weighted images which suggested PVNS to us. Then, the patient underwent knee arthroscopy and biopsy to assist in diagnosis. The arthroscopic appearance and pathology were consistent with PVNS and the hyperplastic synovium was removed during arthroscopy. After the operation, she did active functional exercises and took disease-modifying antirheumatic drugs to control RA. She recovered well and remained asymptomatic after half a year of follow-up. Also, there was no recurrence of the right knee. As we all know, RA is a systemic autoimmune disease characterized by chronic synovitis and joint damage. And PVNS is characterized by synovial proliferation and infiltrative process. Both of them are synovial involvement and the clinical manifestations are quite similar. PVNS has occasionally been reported in association with RA. So it is difficult to make a clear diagnosis of RA combined with PVNS. Literature was searched with RA+PVNS in the WanFang Medical Network Database and China National Knowledge Infrastructure and there were no related Chinese cases. Then we searched literature from PubMed with RA+PVNS. The cases were still rare and eventually 2 related articles were yielded including 2 similar patients. It is necessary to fully understand the disease development, complicated MRI appearance and various pathological morpho-logy. They can contribute to making a correct diagnosis which is effective to guide the proper treatment.
Arthritis, Rheumatoid/diagnosis*
;
Arthroscopy
;
China
;
Female
;
Humans
;
Knee Joint/diagnostic imaging*
;
Magnetic Resonance Imaging
;
Middle Aged
;
Neoplasm Recurrence, Local
;
Synovitis, Pigmented Villonodular/diagnosis*
10.Synchronization of Synovial Chondromatosis and Mycobacterium intracellurae Infection in Olecranon Bursitis: A Case Report
Dong Hyun KIM ; Seunggi MIN ; Hyun Joo LEE ; Hee June KIM ; Hoseok LEE ; Jong Pil YOON
Clinics in Shoulder and Elbow 2019;22(1):46-49
A 73-year-old woman presented with a recurrent cystic mass around her left olecranon. She had a history of 8 steroid injections due to elbow pain beginning 3 years ago and twice had undergone aspiration of olecranon bursitis that developed two months prior to presentation. She had been taking medications for hypertension and diabetes with no pertinent past history. On magnetic resonance imaging (MRI), there were multiple nodules in the olecranon bursa, which were isointense to muscle on T1-weighted images and hyperintense to muscle on T2-weighted images. Our initial diagnosis was synovial chondromatosis. On bursoscopy, masses of gray-white colored nodules were observed in the bursa. Finally, synovial chondromatosis and non-tuberculous mycobacterial infection were concurrently diagnosed. In conclusion, uncalcified synovial chondromatosis and rice bodies can have similar visual and MRI characteristics; therefore, we suggest that clinicians should be aware of the possibility of other infections in cases of this type.
Aged
;
Bursitis
;
Chondromatosis, Synovial
;
Diagnosis
;
Elbow
;
Female
;
Humans
;
Hypertension
;
Magnetic Resonance Imaging
;
Mycobacterium
;
Nontuberculous Mycobacteria
;
Olecranon Process
;
Synovitis
;
Tuberculosis

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