scholarly journals Investigation of the Proinflammatory Cytokines’ Effects in Peripheral Blood and Cartilage Tissue Samples of Knee Osteoarthritis Patients

Author(s):  
Sezen ATASOY
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&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.


2017 ◽  
Vol 17 (2) ◽  
pp. 3-8
Author(s):  
Emils Smitins ◽  
Dace Danberga ◽  
Mara Pilmane ◽  
Ilze Akota

Abstract Introduction. Facial morphogenesis occurs from the fourth to the twelfth gestation week, when the cells from nerve crest migrate to the region of face, forming the primary palate. The cleft palate is an abnormality in embryogenesis period, which is characterized by the absence of fusion of palatal shelves. The incidence of cleft lip and palate is one in 700 live births. In recent years the effect of different genes and signaling molecules, including Runx2, Wnt3 and OPG have been studied in the development of cleft palate, because these substances are considered to be regulators of pathogenesis responsible for formation of bone and cartilage tissue and particularly the bone. Aim of the Study. The aim of the work was to evaluate the expression of Runx2, Wnt3 and OPG in palate bone and nasal cartilage for children with cleft palate. Material and methods.Eleven bone and cartilage samples were obtained from 21 children of the lip, soft and hard palate correction surgery. All the patients were diagnosed with clefts of the lip, alveolar process of maxilla, and palate. In the tissue sections using the immunohistochemistry method (IMH), were determined Runx2 (code: AB192256, 1: 250, Abcam GB, rabbit), Wnt3 (code: AB1992, 1: 800, Abcam GB, rabbit), and OPG (code: A0611, 1: 100, The Orbit USA, rabbit) local expression. We used a semi-quantitative census method for quantifying the positive structures. Results. Runx2 expression was observed in five patient bone tissue samples and six patient cartilage tissue samples. Of the Runx2 positive bone tissue, in one case we observed occasional, in two cases- few, in one case- moderate to numerous and in one case numerous positive osteocytes while in tissue of cartilage in two cases we observed few, in one case- few to moderate, in two casesmoderate, and in one case numerous positive chondrocytes. A significant difference in Wnt3 expiation was observed between bone and cartilage tissues. Wnt3 expressing chondrocytes were observed in all samples, where in one case- occasional, in three cases few, in one case-moderate, and in six cases-numerous positive cartilage cells were observed. The expression of the gene in the bone was observed in nine cases, which contained mostly occasional or few positive structures, except in three cases where in one Wnt3 was marked by few to moderate and in two cases numerous positive osteocytes. OPG expression was observed in all samples, but in the cartilage, the expression was more pronounced. In the cartilage in seven cases, there were numerous positive chondrocytes, in one case- few to moderate, in two cases moderate to numerous and in one case few to moderate number of chondrocytes. OPG showed variable expression. In four cases, we observed occasional to few, in one case few to moderate, in one case- moderate, in one case moderate to numerous and in four cases numerous positive bone cells. Conclusion. Cartilage tissue expresses significantly more Runx2, Wnt3 genes and OPG proteins, indicating a greater compensatory tissue capacity. In the case of palate clefts, the high expression of Wnt3 and OPG and lower expression of Runx2 could indicate a significant tissue proliferation which predominates over mineralization and ossification processes.


Arthritis ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ibrahim Yilmaz ◽  
Nevzat Selim Gokay ◽  
Rifat Bircan ◽  
Gamze V. Saracoglu ◽  
Sergulen Dervisoglu ◽  
...  

Purpose. This study has researched the affect of different methodologies of harvesting and analysing the samples in determining the mediators emerging after the rat articular cartilage injury. Materials and Methods. One hundred and forty-four male wistar rats were divided into 2 groups. Synovial fluid samples were taken from all of the rats. We entered into the right knees of the rats in group I (n=36) under anaesthesia and took cartilage tissue samples from their distal femur. Samples were taken as reference values for enzyme linked immunosorbent assay (ELISA) and histopathological evaluations. We entered into the right knees of the rats in group II (n=108) and formed complete layer of cartilage injury in their medial femoral condyles. At the end of the 15th day, the rats were sacrificed after taking synovial fluid samples from their right knees creating defect in the rats in group II. The molecular markers in the synovial fluid and cartilage tissue samples which were taken from the experimental and control groups (MMP-9, MMP-13, TIMP-1, TNF-α, and NO) were analysed by direct or indirect methodologies. SPSS 18.0 Package program was used in the statistical evaluation. Students t-test where the measurement variables between the experimental and control groups were compared was applied. Receiver Operating Characteristics (ROC) curves were used in the determination of the diagnostic sufficiency from the tissue. Results. No difference was found between TIMP-1 (P=0.67) and MMP-9 (P=0.28) levels in synovial fluid and cartilage tissue. From the molecular markers, when MMP-9, MMP-13, NO, TIMP-1, TNF-α′, the area under ROC curve, and P values were examined, MMP-13 (P<0.0001, 95% CI: 0.70–0.85), NO (P<0.0001, 95% CI: 0.72–0.86), and TNF-α (P<0.0001, 95% CI: 0.91–0.98) results were found to be statistically significant. Inferences. The indirect ELISA protocol which we apply for the cartilage tissue as an alternative to synovial lavage fluid is a reliable method which can be used in the determination of articular cartilage injury markers.


Author(s):  
Tongtong Zhao ◽  
Kai Zhang ◽  
Yelei Zhang ◽  
Yating Yang ◽  
Xiaoshuai Ning ◽  
...  

Abstract Rationale and objective Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. Methods We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. Results Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients’ BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. Conclusion Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.


Author(s):  
Ekin İlke Şen ◽  
Mustafa Aziz Yıldırım ◽  
Tuğba Yeşilyurt ◽  
Fatma Nur Kesiktaş ◽  
Demirhan Dıraçoğlu

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kai-Yang Wang ◽  
Xiang-Yun Jin ◽  
Yu-Hui Ma ◽  
Wei-Jie Cai ◽  
Wei-Yuan Xiao ◽  
...  

Abstract Background Cartilage injury and pathological degeneration are reported in millions of patients globally. Cartilages such as articular hyaline cartilage are characterized by poor self-regeneration ability due to lack of vascular tissue. Current treatment methods adopt foreign cartilage analogue implants or microfracture surgery to accelerate tissue repair and regeneration. These methods are invasive and are associated with the formation of fibrocartilage, which warrants further exploration of new cartilage repair materials. The present study aims to develop an injectable modified gelatin hydrogel. Method The hydrogel effectively adsorbed proteoglycans secreted by chondrocytes adjacent to the cartilage tissue in situ, and rapidly formed suitable chondrocyte survival microenvironment modified by ε-poly-L-lysine (EPL). Besides, dynamic covalent bonds were introduced between glucose and phenylboronic acids (PBA). These bonds formed reversible covalent interactions between the cis−diol groups on polyols and the ionic boronate state of PBA. PBA-modified hydrogel induced significant stress relaxation, which improved chondrocyte viability and cartilage differentiation of stem cells. Further, we explored the ability of these hydrogels to promote chondrocyte viability and cartilage differentiation of stem cells through chemical and mechanical modifications. Results In vivo and in vitro results demonstrated that the hydrogels exhibited efficient biocompatibility. EPL and PBA modified GelMA hydrogel (Gel-EPL/B) showed stronger activity on chondrocytes compared to the GelMA control group. The Gel-EPL/B group induced the secretion of more extracellular matrix and improved the chondrogenic differentiation potential of stem cells. Finally, thus hydrogel promoted the tissue repair of cartilage defects. Conclusion Modified hydrogel is effective in cartilage tissue repair.


Sign in / Sign up

Export Citation Format

Share Document