Ligustrazine Reduces the Apoptosis of Synovial Cells in Knee Arthritis Rats by Inhibiting the Expression of Glucose Regulatory Protein 78 and CCAAT Enhancer Binding Protein Beta (C/EBPb)

2021 ◽  
Vol 13 (8) ◽  
pp. 1467-1473
Author(s):  
Housen Jiang ◽  
Kun Zhang ◽  
Liming Zhao ◽  
Yan Li

To investigate the effect of Ligustrazine on synovial cells and expression of GRP78 and C/EBPb in knee arthritis rats, 52 healthy SD rats, aged 10-15 months, weighing 185–225 g, were selected and fed routinely. According to the principle of random distribution, the experimental rats were assigned into healthy group, arthritis group, ligustrazine 1 and 2 groups, with 13 rats in each group. HE staining was used to detect the pathological morphology. Mankin score was used to measure the severity of the disease. The apoptosis of synovial cells was assessed by flow cytometry. col2α1 and VEGF levels were detected by RT-PCR and GRP78, XBP1 and C/EBP β levels were detected by Western blot. In the healthy group, the cells were scattered orderly, the cartilage surface was smooth, and the synovial tissue was not damaged; in the arthritis group, the joint tissue was damaged, the synovial tissue proliferated and degenerated, the cells were disordered, and synovial pannus was produced; in Ligustrazine group 1 and Ligustrazine 2 groups had certain improvement, and the effect to Ligustrazine group 2 was more obvious. Mankin score of healthy group was lower than arthritis group (P < 0.05) which had higher Mankin score than Ligustrazine 1 and 2 groups, and the Mankin score of Ligustrazine 2 group was lower than that of Ligustrazine 1 group (P < 0.05). Synovial cells apoptosis in healthy group was lower than arthritis group (P < 0.05) which had higher apoptosis than Ligustrazine 1 group and ligustrazine 2 group (P < 0.05) with lower apoptosis for Ligustrazine 2 group (P < 0.05). The expressions of col2α1 mRNA and VEGF mRNA in healthy group were lower than arthritis group (P < 0.05) which had higher levels than Ligustrazine 1 and 2 groups with Ligustrazine 2 group showing more obvious effects (P < 0.05). Arthritis group had significantly elevated levels of GRP78 and XBP1 and decreased C/EBP β levels (P < 0.05). However, GRP78 and XBP1 levels in TMP-1 group and tmp-2 group were decreased and C/EBP β level was increased (P < 0.05). In a word, Ligustrazine can reduce the apoptosis of synovial cells, promote the repair of cartilage tissue and improve the condition of knee arthritis rats by regulating the expression level of GRP78 and XBP1.

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Taku Ukai ◽  
Masato Sato ◽  
Shiho Wasai ◽  
Takumi Takahashi ◽  
Haruka Omura ◽  
...  

Abstract Background Cartilage degeneration is assessed using various methods. Although macroscopic evaluation can directly measure cartilage degeneration, it cannot accurately assess cartilage properties. Histological examination is one of the most accurate methods for evaluating cartilage degeneration. However, it is invasive and requires collection of cartilage tissue. In contrast, the Arthro-BST™ probe can assess cartilage properties noninvasively. This study aimed to evaluate the effectiveness of the Arthro-BST in assessing cartilage degeneration by comparing macroscopic (International Cartilage Repair Society [ICRS] classification) and histological evaluations (modified Mankin score and Osteoarthritis Research Society International [OARSI] histological grade). Methods Fourteen femoral heads were excised from 13 patients during surgery to treat hip osteoarthritis or femoral fracture. The ICRS score was used for macroscopic evaluation of cartilage degeneration. The Arthro-BST was applied at sites matching the areas of cartilage damage. The sites assessed using the ICRS classification and Arthro-BST were evaluated histologically (modified Mankin score and OARSI histological grade), and these were compared with the Arthro-BST results. Results The ICRS classification identified significant differences between grades 1 and 3 (p < 0.01), between grades 1 and 4 (p < 0.01), between grades 2 and 3 (p < 0.01), and between grades 2 and 4 (p < 0.01). Significant correlations were observed between the Arthro-BST results and the ICRS score, modified Mankin score (structure, cellularity, matrix staining, total score), and OARSI histological grade. Conclusions In the assessment of hip osteoarthritis, the Arthro-BST results correlated with those of macroscopic and histological evaluations. The Arthro-BST is useful for assessing hip osteoarthritis and may be helpful for noninvasive assessment of cartilage degeneration.


1996 ◽  
Vol 48 (4) ◽  
pp. 243-247 ◽  
Author(s):  
J. Rödel ◽  
E. Straube ◽  
W. Lungershausen ◽  
A. Roth ◽  
A. Groh

2020 ◽  
Vol 10 (2) ◽  
pp. 239-245
Author(s):  
Zhendong Liu ◽  
Kongbin Zhang ◽  
Yuesong Weng ◽  
Jianqiang Huang ◽  
Lu You

Objective: Resveratrol (Resv) is a polyphenolic compound with anti-inflammatory, anti-oxidant, and other pharmacological effects in rheumatoid arthritis (RA). However, whether Resv has protective and therapeutic effects in post-traumatic arthritis (PTA) remains poorly understood. We explored the function of Resv in the treatment of PTA and reducing chondrocyte matrix degradation and chondrocyte apoptosis in PTA rats. Methods: The PTA rat model was established and divided into sham group and Resv gavage group. MMP-13 and Hyp contents in the joint cavity fluid were tested by ELISA. MMP-13 and COL2A1 protein expressions in the articular cartilage tissue were detected by Western blot. Mankin score was measured. The chondrocytes cultured in vitro and divided into control group, IL-1β group, and IL-1β + Resv group. Flow cytometry was adopted to detect cell apoptosis. Results: MMP-13 and Hyp contents were significantly increased, MMP-13 protein expression was significantly upregulated, COL2A1 protein expression was significantly reduced, while Mankin score was increased in PTA group in comparison to those in normal rats. Resv treatment significantly reduced MMP-13 protein expression and elevated COL2A1 protein level in cartilage tissue, decreased MMP-13 and Hyp contents in joint cavity fluid, and reduced Mankin score. After the treatment of IL-1β, the level of MMP-13 protein was significantly elevated, with decreased COL2A1 protein level in chondrocytes, and enhanced chondrocytes apoptosis. Resv intervention significantly inhibited MMP-13 protein and increased COL2A1 level in chondrocytes, and attenuated cell apoptosis. Conclusion: Resv inhibits MMP-13 expression, attenuates chondrocyte matrix degradation and apoptosis, indicating it plays a therapeutic value in treating PTA.


Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2413-2418 ◽  
Author(s):  
Mikihiro Yoshie ◽  
Eri Miyajima ◽  
Satoru Kyo ◽  
Kazuhiro Tamura

Local hypoxia that occurs during menstruation triggers angiogenesis that is crucial for cyclical remodeling of the endometrium during the menstrual cycle. Hypoxia is thought to be important for the expression of vascular endothelial growth factor (VEGF) via its transcriptional factor, hypoxia inducible factor (HIF)-1α, in the endometrium. The activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway may modulate HIF-1α protein levels. Stathmin, a microtubule regulatory protein, was expressed in the stroma, glandular epithelium, and vascular endothelium in human endometrium. In this study, we examined a possible role of stathmin in hypoxia-induced HIF-1α and VEGF expression in primary isolated and immortalized human endometrial stromal cells, glandular epithelial cells, and human umbilical venous endothelial cells (HUVEC). Knocking down stathmin expression using small interfering RNA caused microtubule stabilization and inhibited hypoxia-induced VEGF mRNA expression via the reduction of HIF-1α protein levels in endometrial cells and HUVEC. Treatment of the cells with a PI3K inhibitor, wortmannin, inhibited the expression of VEGF mRNA and the accumulation of HIF-1α protein. Silencing of stathmin expression repressed the activation (phosphorylation) of Akt in endometrial cells and HUVEC. These results suggest that endometrial stathmin is linked to HIF-1α protein accumulation and VEGF expression through the PI3K/Akt signaling pathway and may be involved in regeneration of the endometrium during the menstrual cycle in human uterine cells.


2021 ◽  
Vol 12 ◽  
Author(s):  
Anmin Ruan ◽  
Qingfu Wang ◽  
Yufeng Ma ◽  
Dong Zhang ◽  
Lili Yang ◽  
...  

Knee osteoarthritis (KOA) is a chronic degenerative bone and joint disease, which is often clinically manifested as pain, joint swelling, and deformity. Its pathological manifestations are mainly synovial inflammation and cartilage degeneration. This study aims to investigate the efficacy of electro-acupuncture (EA) on model rabbits with varying degrees of KOA and to study the mechanism of EA on KOA based on the innate immune response. Mild and moderate rabbit KOA models were established using a modified Hluth method, and EA was given to both the mild and moderate model groups. The Lequesne-MG index was used to evaluate the behavioral changes in the rabbits before and after EA treatment. Morphological changes in the synovial membrane and cartilage of each group were observed by H&amp;E staining. The Mankin scoring standard and the Krenn scoring standard were used to score the pathology of the cartilage tissue and synovial tissue, respectively. The inflammatory factors and metalloproteinases were detected in the serum of each group by ELISA. The protein and messenger RNA (mRNA) expressions of important elements related to Toll-like receptors (TLRs)-mediated innate immune response in the synovial tissue were detected by Western blot and quantitative PCR (qPCR). The Lequesne-MG index score of the rabbits gradually increased with the modeling prolonged but decreased significantly after EA treatment, indicating that EA has a better effect on alleviating the pain and improving the dysfunction. The morphological analysis showed that the inflammation of and the damage to the synovial membrane and the cartilage tissue gradually deteriorated with the modeling prolonged. However, the synovial membrane inflammation was significantly relieved after EA treatment, and the cartilage injury showed signs of repair. The ELISA analysis showed that, with the modeling prolonged, the serum-related inflammatory factors and mechanism of metalloproteinases gradually increased but decreased after EA treatment. The tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and matrix metalloproteinase3 (MMP3) of EA1 group were significantly lower than those of EA2 group. Both Western blot and qPCR results showed that the protein and mRNA expressions of the elements related to the innate immune response in the synovial membrane increased gradually with the modeling prolonged, but decreased significantly after EA treatment. Additionally, the expression of some components in EA1 group was significantly lower than that in EA2 group. These results confirm that synovial inflammation gradually aggravated with time from the early to mid-stage of KOA. EA alleviated the inflammation and histological changes in KOA rabbits by inhibiting the TLRs-mediated innate synovial immune response. This suggests that using EA in the early stage of KOA may achieve a desirable efficacy.


2021 ◽  
Author(s):  
Ding Liang ◽  
Torsten Lowin ◽  
Xinkun Cheng ◽  
Tim Classen ◽  
Georg Pongratz

Abstract Background: Rheumatoid arthritis (RA) is influenced by the activity of the sympathetic nervous system (SNS). In animal models of RA, the SNS promotes severity of the disease and its manipulation modulates experimental arthritis depending on timing of the intervention. Synovial fibroblasts (SF) are major contributors to RA pathology but their modulation by the SNS has been rarely investigated. In this study we assessed the expression and function of adrenergic receptors in RA and osteoarthritis (OA) synovial fibroblasts and investigated their downstream signaling. Methods: We used western blot and quantitative PCR (qPCR) to determine protein and mRNA of adrenergic receptors in OASF/RASF. Furthermore we determined α1a and β2 protein in synovial tissue by immunofluorescence. ELISA was employed to determine IL-6 production. p38 kinase activation and translocation was analyzed by cell-based ELISA and immunofluorescence.Results: We detected α1a, α2b, β1, β2 and β3 protein in OASF/RASF and α1a and β2 protein in synovial tissue of OA and RA patients. The pro-inflammatory cytokines IFN-γ and TNF downregulated β3 adrenergic receptor. Activation of α1a, α2b, β2 and β3 increased production of TNF-induced IL-6 which was inhibited by specific antagonists. Furthermore, β3 agonism enhanced p38 phosphorylation and translocation to the nucleus.Conclusion: Among a comprehensive characterization of the adrenergic system of OASF/ RASF, we report for the first time β3 expression and demonstrated that this adrenergic receptor participates in the inflammatory response of synovial fibroblasts. Therefore, modulation of β3 might pose a new therapeutic opportunity to modulate synovial fibroblast function in patients with RA.


Folia Medica ◽  
2019 ◽  
Vol 61 (1) ◽  
pp. 90-96
Author(s):  
Nina Staneva Stoyanova ◽  
Marieta Konareva-Kostianeva ◽  
Vesela Mitkova-Hristova ◽  
Irina Angelova

Abstract Aim: To establish the correlation between intraocular pressure (IOP) and thickness of extraocular muscles (EOM), the severity and activity of thyroid-associated orbitopathy (TAO). Materials and methods: 50 patients with TAO were included in the study. They all underwent a thorough ophthalmic examination, Goldmann tonometry (mm Hg) and computer tomography of the orbits, the muscle thickness sum (MTS) of each eye being measured in millimeters. According to the activity of TAO, the patients were divided into two groups – with and without activity, and according to the severity of the disease – into 6 groups: Group 1 (‘O’) had only subjective symptoms, group 2 (‘S’) had soft tissue symptoms, group 3 (‘P’) – proptosis, group 4 (‘E’) – ocular motility disorders, group 5 (‘C’) – corneal damage, and group 6 (‘Si’) – visual impairment; Results: TAO activity was registered in 21 patients (42 eyes, 42%) with MTS 23.39±3.81 and IOP 18.43±4.16. Twenty-nine patients (58 eyes, 58%) with MTS 19±3.21 and IOP 15.98±4.59 showed no TAO activity. The IOP within the groups, in terms of severity, was as follows: group 1 – 19.92+4.05; group 2 – 14.5±2.55; group 3 – 18.04±4.51; group 4 – 18.2±5.05; group 5 – 20.5±4.5; group 6 – 21.5±4.95. A correlation between the IOP and MTS was found. Conclusions: The IOP in patients with TAO depends on the thickness of the EOM, as well as on the activity and severity of the disease.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jun Zhu ◽  
Chengguo Su ◽  
Yuzhou Chen ◽  
Xinyu Hao ◽  
Jianzhen Jiang

Introduction. The hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) play a key role in synovial angiogenesis in rheumatoid arthritis (RA). Therefore, this study aimed to test the hypothesis that electroacupuncture (EA) may inhibit RA synovial angiogenesis via HIF-1α/VEGF expression. Methods. Sprague-Dawley rats were randomly distributed to 4 groups: control, adjuvant arthritis (AA), AA+electroacupuncture (AA+EA), and AA+sham EA groups. AA model was induced by injection of Freund's complete adjuvant in bilateral hind footpad. 3 days after injection, EA was delivered to the acupoints Zusanli (ST 36) and Xuanzhong (GB 39) once every two days for a total of 8 times in the AA+EA group, while sham EA treatment was applied in the AA+sham EA group. The arthritis score, paw volume, and H&E staining for each animal were measured. CD34 expression in synovial tissue of ankle joint was observed by immunohistochemistry. HIF-1α and VEGF mRNA and protein levels in synovial tissue were determined by real-time quantitative PCR and Western blot, respectively. Results. Compared with rats in AA group, EA stimulation significantly decreased arthritis scores, paw volume, and pathological damage of synovial tissues. Moreover, EA markedly suppressed the synovial angiogenesis of AA rats, as evidenced by reduced CD34 positive expression. Furthermore, EA significantly reduced HIF-1α and VEGF mRNA and protein levels in synovial of AA rats. Finally, the CD34 expression in synovial tissue was positively correlated with HIF-1α and VEGF protein levels. Conclusion. EA on ST36 and GB39 acupoints can effectively inhibit synovial angiogenesis in the AA rat model via downregulating HIF-1α/VEGF expression.


Author(s):  
T. M. Vidhyalakshmi ◽  
S. K. Raval ◽  
P. V. Parikh ◽  
P. V. Patel

Equine theileriosis, an OIE listed disease caused by Theileria equi is an economically important haemoprotozoan disease of horses in tropical and subtropical parts of the world. The aim of the present study was to monitor the biochemical alterations in order to find out the severity of the disease. Standard assay kits were used to study the biochemical parameters of horses positive for theileriosis in comparison with healthy ones. Out of 75 serum samples, 25 samples were collected from horses positive for theileriosis and 50 from healthy horses. The serum levels of GPT (32.00±2.30 U/L), GOT (350.84±27.87 U/L), GGT (20.95±0.92 U/L), LDH (823.74±102.93 U/L), total protein (8.11±0.37 g/dl), globulin (3.84±0.40 g/dl), BUN (46.26±5.27 mg/dl) and creatinine (1.33±0.18 mg/dl) were found to be significantly increased (p less than 0.01) in infected horses compared to the healthy group. Non- significant elevation (p greater than 0.05) in total bilirubin (1.08±0.14 mg/dl), unconjugated bilirubin (0.57±0.11 mg/dl) and glucose (102.57±30.41 mg/dl) as well as non-significant reduction (p>0.05) in conjugated bilirubin (0.42±0.04 mg/dl), albumin (4.26±0.24 g/ dl) and A/G ratio (1.55±0.30) were also observed in infected group. There was no significant alteration (p>0.05) in the level of serum calcium (12.32±0.36 mg/dl) and phosphorus (4.53±0.33 mg/dl), as compared to the healthy group. Significant elevation of GOT, GPT, GGT, BUN and creatinine revealed the involvement of liver and kidney functions in T. equi infected horses.


Sign in / Sign up

Export Citation Format

Share Document