scholarly journals Targeting Soluble Epoxide Hydrolase and Cyclooxygenases Enhance Joint Pain Control, Stimulate Collagen Synthesis, and Protect Chondrocytes From Cytokine-Induced Apoptosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Laura Tucker ◽  
Troy N. Trumble ◽  
Donna Groschen ◽  
Erica Dobbs ◽  
Caroline F. Baldo ◽  
...  
Keyword(s):  
Pain Control ◽  
Joint Pain ◽  
Collagen Synthesis ◽  
Inertial Sensors ◽  
Joint Inflammation ◽  
Chondrocyte Apoptosis ◽  
Cox Inhibitors ◽  
Cox Inhibitor ◽  
Tnf Α ◽  
Radiocarpal Joint

Objective: To determine the symptomatic and disease-modifying capabilities of sEH and COX inhibitors during joint inflammation.Methods: Using a blinded, randomized, crossover experimental design, 6 adult healthy horses were injected with lipopolysaccharide (LPS; 3 μg) from E. coli in a radiocarpal joint and concurrently received the non-selective cyclooxygenase (COX) inhibitor phenylbutazone (2 mg/kg), the sEH inhibitor t-TUCB (1 mg/kg) or both (2 mg/kg phenylbutazone and 0.1, 0.3, and 1 mg/kg t-TUCB) intravenously. There were at least 30 days washout between treatments. Joint pain (assessed via inertial sensors and peak vertical forces), synovial fluid concentrations of prostanoids (PGE2, TxB2), cytokines (IL-1β, IL-6, TNF-α) and biomarkers of collagen synthesis (CPII) and degradation (C2C) were measured at pre-determined intervals over a 48-h period. The anti-apoptotic effect of COX and sEH inhibitors was determined via ELISA technique in primary equine chondrocytes incubated with TNF-α (10 ng/ml) for 24 h. Apoptosis was also determined in chondrocytes incubated with sEH-generated metabolites.Results: Combined COX and sEH inhibition produced significantly better control of joint pain, prostanoid responses, and collagen synthesis-degradation balance compared to each compound separately. When administered separately, pain control was superior with COX vs. sEH inhibition. Cytokine responses were not different during COX and/or sEH inhibition. In cultured chondrocytes, sEH inhibition alone or combined with COX inhibition, but not COX inhibition alone had significant anti-apoptotic effects. However, sEH-generated metabolites caused concentration-dependent apoptosis.Conclusions: Combined COX and sEH inhibition optimize pain control, attenuate loss of articular cartilage matrix during joint inflammation and cytokine-induced chondrocyte apoptosis.

Evaluating the efficacy of intra-articular injections of platelet rich plasma (PRP) in rheumatoid arthritis patients and its impact on inflammatory cytokines, disease activity and quality of life.

2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Platelet Rich Plasma ◽  
Joint Inflammation ◽  
Monthly Interval ◽  
Post Injection ◽  
Tnf Α

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.

scholarly journals Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1022
Author(s):  
Tatyana P. Makalish ◽  
Ilya O. Golovkin ◽  
Volodymyr V. Oberemok ◽  
Kateryna V. Laikova ◽  
Zenure Z. Temirova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Rat Model ◽  
Peripheral Blood ◽  
Antisense Oligonucleotide ◽  
Joint Inflammation ◽  
Blood Concentrations ◽  
Tnf Α ◽  
Effective Drugs ◽  
First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

scholarly journals Intracellular versus extracellular inhibition of calpain I causes differential effects on pain in a rat model of joint inflammation

2021 ◽  
Vol 17 ◽  
pp. 174480692110161
Author(s):  
Jason J McDougall ◽  
Miranda McConnell ◽  
Allison R Reid
Keyword(s):  
Joint Pain ◽  
Acute Inflammation ◽  
Weight Bearing ◽  
Joint Inflammation ◽  
Local Administration ◽  
Calpain Inhibitor ◽  
Mast Cell Tryptase ◽  
Calcium Dependent ◽  
Protease Activated Receptor 2 ◽  
Arthritic Joints

Calpain I is a calcium-dependent cysteine protease which has dual effects on tissue inflammation depending on its cellular location. Intracellularly, calpain I has pro-inflammatory properties but becomes anti-inflammatory when exteriorised into the extracellular space. In this study, the effect of calpain I on joint pain was investigated using the kaolin/carrageenan model of acute synovitis. Evoked pain behaviour was determined by von Frey hair algesiometry and non-evoked pain was measured using dynamic hindlimb weight bearing. Local administration of calpain I reduced secondary allodynia in the acute inflammation model and this effect was blocked by the cell impermeable calpain inhibitor E-64c. Calpain I also blocked the algesic effect of the protease activated receptor-2 (PAR-2) cleaving enzyme mast cell tryptase. The cell permeable calpain blocker E-64d also produced analgesia in arthritic joints. These data suggest that calpain I produces disparate effects on joint pain viz. analgesia when present extracellularly by disarming PAR-2, and pro-algesic when the enzyme is inside the cell.

scholarly journals Research Progress on Acupuncture Treatment of Knee Osteoarthritis

2021 ◽  
Vol 9 (4) ◽  
pp. 106-110
Author(s):  
Zhang Yueyu ◽  
Song Aiqun ◽  
Peng Ying
Keyword(s):  
Acupuncture Therapy ◽  
Knee Joint ◽  
Knee Osteoarthritis ◽  
Joint Pain ◽  
Acupuncture Treatment ◽  
Treatment Plan ◽  
Joint Inflammation ◽  
Research Progress ◽  
Osteoarthritis Of The Knee ◽  
Joint Function

Osteoarthritis of the knee is a common clinical degenerative disease, which occurs in middle-aged and elderly people. Acupuncture therapy has a significant effect in the treatment of knee osteoarthritis, and is gradually accepted by more and more patients. Observing the treatment of knee osteoarthritis by different acupuncture and moxibustion therapies, we can find that acupuncture treatment of knee osteoarthritis has the advantages of relieving knee joint pain, improving knee joint function, absorbing knee joint inflammation, and promoting the recovery of damaged soft tissue. The treatment of osteoarthritis provides a more effective treatment plan.

scholarly journals EVALUATION OF AQUEOUS FRUIT EXTRACT OF TAMARINDUS INDICA (L) FOR INHIBITION OF TUMOR NECROSIS FACTOR-a AND CYCLO OXYGENASE ENZYMES IN EXPERIMENTAL ANIMAL

2018 ◽  
Vol 11 (3) ◽  
pp. 57 ◽  
Author(s):  
Mohammad Daud Ali ◽  
Atul Kumar Gupta ◽  
Arif Naseer ◽  
Mohd Aamir Mirza ◽  
Sabir Afzal
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Significant Inhibition ◽  
Tamarindus Indica ◽  
Screening Assay ◽  
Standard Drug ◽  
Cox Inhibitor ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Necrosis Factor

 Objective: The main objective of this study was to assess tumor necrosis factor-α (TNF)-α and cyclooxygenase enzymes (COX) inhibition potency of Tamarindus indica Linn. in comparison to standard drug (indomethacin).Methods: Three plants are selected for the studies, namely: Aloe vera (L.), Terminalia chebula Reitz., and T. indica Linn. Estimation of TNF-α in serum (at 1:10 dilution in PBS) was performed using the immunoenzymatic (ELISA) technique. COX inhibitor screening assay kits were used for estimation of COX.Result: All three plant extracts showed a potent significant inhibition of the COX enzyme as compared to the positive control and standard drug when the animal was administered with 400 mg/kg. These studies indicate that the T. indica plant extract showed significant COX inhibition even at low dose. All the extracts were effective anti-inflammatory in nature, however, T. indica extracts at a dose of 400 mg/kg were found to be most potent. It was found to be comparable with that of Indomethacin 10 mg/kg body weight.Conclusion: The anti-inflammatory activity expressed by all the three plants A. vera (L.), T. chebula Reitz., and T. indica L. Among all three plants T. indica (L) was found to be more active against both TNF-α and COX, and it was comparable to standard drug Indomethacin. Need further studies to elucidate the exact secondary metabolite by which these plants express this activity.

LncRNA PVT1 induces chondrocyte apoptosis through upregulation of TNF-α in synoviocytes by sponging miR-211-3p

2020 ◽  
Vol 52 ◽  
pp. 101560 ◽  
Author(s):  
Kai Xu ◽  
Zhen Meng ◽  
Xin-miao Xian ◽  
Mo-hong Deng ◽  
Qing-gong Meng ◽  
...  
Keyword(s):  
Chondrocyte Apoptosis ◽  
Tnf Α

scholarly journals miR-27b-3p Targeting BDNF Inhibits the TrkB/CREB Signaling Pathway and Improves IL-1 β-Induced Chondrocyte Inflammation

2021 ◽  
Author(s):  
cailian ruan ◽  
Rui jun CONG ◽  
Miao Wang ◽  
LI JUN WANG ◽  
YONG YU ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Cartilage Degradation ◽  
Camp Response Element Binding ◽  
Detection Methods ◽  
Chondrocyte Apoptosis ◽  
Cell Transfection ◽  
Expression Levels ◽  
Tnf Α ◽  
Safranin O

Abstract Background: Explore the mechanism of "miR-27b-3p targeting BDNF inhibits the TrkB/CREB signaling pathway and improves IL-1 β-induced chondrocyte inflammation".Methods: The animal and cell models of arthritis were constructed, and various biochemical detection methods were used to detect the changes of apoptosis, inflammation and oxidative stress.Results: The results showed that the expression of miR-27b-3p was downregulated in IL-1β-treated chondrocytes and cartilage tissues isolated from a KOA rat model. miR-27b-3p overexpression notably reduced IL-1β-induced chondrocyte apoptosis and the expression levels of caspase-3 and caspase-9. In addition, cell transfection with miR-27b-3p mimics increased the mRNA and protein expression levels of inducible nitric oxide synthase and cyclooxygenase-2. The levels of nitric oxide, prostaglandin E2 (PGE2), TNF-α and IL-6 were also reduced following cell transfection with miR-27b-3p mimics. Furthermore, bioinformatics analysis predicted that miR-27b-3p could directly target brain-derived neurotrophic factor (BDNF). Additionally, the present study suggested that the tropomyosin receptor kinase B (TrkB)/cAMP response‑element binding protein (CREB) signaling axis could be a downstream pathway of the miR-27b-3p/BDNF axis. The percentage of apoptotic cells and the expression levels of nitric oxide, PGE2, TNF-α and IL-6 were enhanced in chondrocytes co-treated with BDNF + IL-1β. However, these effects were restored following transfection of chondrocytes with miR-27b-3p mimics. Staining of cartilage tissues with safranin O showed that miR-27b-3p overexpression Significantly attenuated KOA-induced cartilage degradation.Conclusions:miR-27b-3p targeting BDNF inhibits the TrkB/CREB signaling pathway and improves IL-1 β-induced chondrocyte inflammation.

scholarly journals Percutaneous Radiofrequency Hip Joint Denervation

2021 ◽  
Author(s):  
Nieves Saiz-Sapena ◽  
Vicente Vanaclocha-Vanaclocha ◽  
José María Ortiz-Criado ◽  
Leyre Vanaclocha
Keyword(s):  
Quality Of Life ◽  
Pain Relief ◽  
Hip Joint ◽  
Pain Control ◽  
Joint Pain ◽  
Pulsed Radiofrequency ◽  
Total Hip ◽  
Sensory Denervation ◽  
Hip Arthroplasties

With an aging population, chronic osteoarthritic hip joint pain is becoming a major issue. Most patients with hip pain can control their pain with conservative measures but with a gradual reduction in their quality of life. When gradually reduced ambulation and pain become recalcitrant, total hip arthroplasty is the next step. For most patients, this is a good way to improve pain control and to recover some quality of life, but for a few this aggressive surgical procedure is not possible. Sometimes co-morbidities make total hip arthroplasties undesirable. At other times, the age of the patients recommends to wait for a while. In these cases, other options have to be explored. Percutaneous partial hip joint sensory denervation has become a notable option as it can provide acceptable rates of pain relief with minimal surgical aggressiveness. There are three modalities to perform it: thermal, cooled and pulsed radiofrequency.

scholarly journals PKR Promotes Oxidative Stress and Apoptosis of Human Articular Chondrocytes by Causing Mitochondrial Dysfunction through p38 MAPK Activation—PKR Activation Causes Apoptosis in Human Chondrocytes

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 370 ◽  
Author(s):  
Ching-Hou Ma ◽  
Chin-Hsien Wu ◽  
I-Ming Jou ◽  
Yuan-Kun Tu ◽  
Ching-Hsia Hung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
P38 Mapk ◽  
Articular Chondrocytes ◽  
Cartilage Degeneration ◽  
The Elderly ◽  
Human Articular Chondrocytes ◽  
Poly I:C ◽  
Chondrocyte Apoptosis ◽  
Tnf Α

Osteoarthritis (OA) is one of the most common types of arthritis in the elderly people. It has been known that chondrocyte apoptosis occurs in OA cartilage; however, the detailed molecular mechanism remains unclear. In the current study, we aimed to elucidate the role of double-stranded RNA-dependent protein kinase R (PKR) in the TNF-α-caused apoptosis in chondrocytes. Human articular chondrocytes were digested from cartilages of OA subjects who accepted arthroplastic knee surgery. Our results showed that phosphorylation of p38 MAPK was increased after TNF-α stimulation or PKR activation using poly (I:C), and TNF-α-induced p38 MAPK upregulation was inhibited by PKR inhibition, suggesting phosphor-p38 MAPK was regulated by PKR. Moreover, we found that PKR participated in the p53-dependent destruction of AKT following activation of p38 MAPK. The inhibition of AKT led to the reduced expression of PGC-1α, which resulted in mitochondrial dysfunction and increased oxidative stress. We showed that the reduction of oxidative stress using antioxidant Mito TEMPO lowered the TNF-α-induced caspase-3 activation and TUNEL-positive apoptotic cells. The diminished apoptotic response was also observed after repression of PKR/p38 MAPK/p53/AKT/PGC-1α signaling. Taken together, we demonstrated that the aberrant mitochondrial biogenesis and increased oxidative stress in chondrocytes after TNF-α stimulation were mediated by PKR, which may contribute to the chondrocyte apoptosis and cartilage degeneration in OA.

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