scholarly journals Blocking of checkpoint receptor PD-L1 aggravates osteoarthritis in macrophage-dependent manner in the mice model

2019 ◽  
Vol 33 ◽  
pp. 205873841882076 ◽  
Author(s):  
Shenghou Liu ◽  
Jiqiang Mi ◽  
Wenguang Liu ◽  
Shipeng Xiao ◽  
Chunzheng Gao
Keyword(s):  
Inflammatory Cytokine ◽  
Cruciate Ligament ◽  
Mrna Level ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Mice Model ◽  
Safranin O ◽  
Factor Α

As a chronic degenerative joint disease, osteoarthritis is among the most common diseases all over the world. In osteoarthritis, inflammation plays an important role in the generation of joint symptoms and the development of disease. When the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is blocked, the antitumor immunity will be enhanced. We aim to illustrate the function of PD-L1 in osteoarthritis. Osteoarthritis in mice was induced by the injection of collagenase or anterior cruciate ligament transection (ACLT). Anti-PD-L1 was employed to block the signal of PD-L1. Knee joints histological sections were stained by Safranin-O. The level of cytokine was checked by enzyme-linked immunosorbent assay (ELISA) and mRNA level was shown by quantitative reverse transcriptase polymerase chain reaction. The blockade of PD-L1 signal up-regulated inflammatory response and promoted the development of osteoarthritis in mice. The inflammatory cytokine interleukin-6 and tumor necrosis factor-α expression were promoted by PD-L1 blocking in macrophages. Osteoarthritis was aggravated when the expression of inflammatory cytokine is elevated in macrophages. Our results indicated that the blockade of PD-L1 signal in macrophages elevates the expression of inflammatory cytokine and promotes the development of osteoarthritis in mice, which could be utilized as a potential diagnostic and therapeutic target for osteoarthritis patients.

Measurement of the tibial plateau angle in cats with and without cranial cruciate ligament rupture

2009 ◽  
Vol 22 (02) ◽  
pp. 83-86 ◽  
Author(s):  
S. Reese ◽  
K. Lorinson ◽  
D. Lorinson ◽  
E. Schnabl
Keyword(s):  
Tibial Plateau ◽  
Cruciate Ligament ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Cranial Cruciate Ligament ◽  
Ligament Rupture ◽  
Cruciate Ligament Rupture ◽  
Inter Observer Variability ◽  
Measurement Results ◽  
Cranial Cruciate Ligament Rupture

SummaryThe objective of the present study was to determine the tibial plateau angle (TPA) in cats without stifle pathology and to compare it with cats suffering from an isolated cranial cruciate ligament rupture. Mediolateral radiographs of the stifle were taken and the tibial plateau angle was measured based on the method previously described by Slocum and Devine (1983) for dogs. Three observers with different levels of experience evaluated the radiographs of all of the cats in this study. The mean tibial plateau angle measured by all three observers in the cats with a rupture of the cranial cruciate ligament (CCL) was 3.1° greater than in cats without stifle pathology. Neither gender, age, body weight nor degenerative joint disease had an influence on measurement results. The authors found an inter-observer variability of ± 5.3°. Hence it can be concluded that cats with cranial cruciate ligament rupture have a greater TPA, and this at least lends some credence to the possibility of higher TPA being a predis-posing factor for cruciate injury in this species.

Neurogenic origin of articular hyperemia in early degenerative joint disease

1999 ◽  
Vol 276 (3) ◽  
pp. R745-R752 ◽  
Author(s):  
Jason J. McDougall ◽  
William R. Ferrell ◽  
Robert C. Bray
Keyword(s):  
Joint Instability ◽  
Cruciate Ligament ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Calcitonin Gene ◽  
Neurogenic Origin ◽  
Vasomotor Activity ◽  
Anterior Cruciate ◽  
Supporting Structures ◽  
Acl Transection

It has been speculated that joint instability resulting from anterior cruciate ligament (ACL) rupture could be exacerbated by changes in vasomotor activity in the remaining supporting structures. In this study, the effect of ACL transection on medial collateral ligament (MCL) basal perfusion and its responsiveness to calcitonin gene-related peptide (CGRP) and sympathetic adrenergic influences was examined. Using urethan-anesthetized rabbits, we tested the effects of CGRP and its antagonist CGRP-(8—37) by topical application of these agents to the exposed knee while sympathetic influences were tested by electrically stimulating the saphenous nerve. It was found that MCL basal perfusion was elevated in ACL-sectioned joints; however, this effect was abrogated by prior resection of the articular nerve supply. At the doses tested, the normal vasodilator response to CGRP was abolished in ACL-sectioned joints, whereas the response to CGRP-(8—37) was attenuated. Even under the influence of increased constrictor tone, MCL and capsule blood vessels still showed substantially reduced responses to exogenous CGRP administration. By contrast, nerve-mediated constrictor responses were mostly unaffected by joint instability. This study suggests that posttraumatic knee joint hyperemia is neurogenically mediated, possibly by increased secretion of CGRP.

scholarly journals Chondroprotective Activity ofMurraya exoticathrough Inhibitingβ-Catenin Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Longhuo Wu ◽  
Haiqing Liu ◽  
Rui Zhang ◽  
Linfu Li ◽  
Jialin Li ◽  
...  
Keyword(s):  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Chondrocyte Apoptosis ◽  
Dependent Manner ◽  
Chain Reaction ◽  
Protein Expressions ◽  
Murraya Exotica ◽  
Oa Chondrocytes ◽  
Polymerase Chain ◽  
Dose Dependent

Osteoarthritis (OA) is a degenerative joint disease that affects millions of people. Currently, there is no effective drug treatment for it. The purpose of this study is to investigate the chondroprotective effects ofMurraya exotica(L.) on OA. The rat OA models were duplicated to prepare for separating OA chondrocytes, synovial fluid (SF), and serum containingM. exotica(50 mg/kg, 100 mg/kg, and 200 mg/kg),M. exoticashowed the activity of decreasing the contents of TNF-αand IL-1βin SF and the chondrocyte apoptosis in a dose-dependent manner. To investigate the probable mechanism, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to determine gene expression and protein profiles, respectively. The results reveal thatM. exoticacan downregulate mRNA and protein expressions ofβ-catenin and COX-2 and reporter activity significantly. Conclusively,M. exoticaexhibits antiapoptotic chondroprotective activity probably through inhibitingβ-catenin signaling.

Association of mineralisations in the stifle joint of domestic cats with degenerative joint disease and cranial cruciate ligament pathology

2016 ◽  
Vol 19 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Katja Voss ◽  
Philemon Karli ◽  
Pierre M Montavon ◽  
Hans Geyer
Keyword(s):  
Medial Meniscus ◽  
Cruciate Ligament ◽  
Degenerative Joint Disease ◽  
Joint Capsule ◽  
Degenerative Changes ◽  
Joint Disease ◽  
Fat Pad ◽  
Cranial Cruciate Ligament ◽  
Stifle Joint ◽  
Periarticular Tissue

Objectives The aim of the study was to evaluate the prevalence, size, location and appearance of mineralisations in feline stifle joints, and to evaluate their relationship with osteoarthritis and cranial cruciate ligament (CrCL) status. Methods Presence or absence, and size of mineralisations were determined from lateral stifle radiographs of 25 cats with CrCL rupture, and 44 cat cadavers without CrCL rupture. Mineralisations were classified as small, medium or large. Prevalence was compared between the clinically affected cats and the cadavers; the cadaver group was subdivided into an age-matched and an older group. Ten stifles with varying sizes of mineralisations were prepared as whole-knee specimens for histopathology. Location and appearance of the mineralisations, and degenerative changes in the cruciate ligaments, menisci, articular cartilage and joint capsule are described. Results Prevalence of articular mineralisations was 0.76 in stifles of cats with CrCL rupture (mean ± SD age 8.6 ± 4.5 years), 0.64 in stifles of age-matched cat cadavers and 0.74 in older cat cadavers (mean ± SD age 17.0 ± 2.4 years). Cats with CrCL rupture had a higher percentage of medium and large mineralisations than cats without CrCL rupture. Microscopically, small mineralisations were calcifications usually located in the cranial horn of the medial meniscus. Larger mineralisations were found to be ossifications, commonly located in the joint capsule and fat pad. Cats with larger mineralisations showed more signs of osteoarthritis, including degenerative changes in the CrCL. Conclusions and relevance Mineralisations in feline stifle joints were found to differ in size, appearance and location. Small mineralisations were usually confined to the medial meniscus, as described previously; larger mineralisations tended to be located in the tissues cranial to the menisci and seemed to be associated with osteoarthritis and CrCL pathology. Large mineralisations in feline stifles are ossifications in periarticular tissue and are associated with degenerative joint disease.

NEAT1 attenuates osteoarthritis development by sponging miR-424-5p and up-regulating SMAD7 expression

2020 ◽  
Author(s):  
Dezhi Zhang ◽  
Lin Song ◽  
Xiaohe Wang
Keyword(s):  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Mrna Level ◽  
Joint Disease ◽  
Inflammatory Factors ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Smad7 Expression ◽  
Development Methods ◽  
Pro Inflammatory Cytokines

Abstract Background: Osteoarthritis is extensively accepted as a chronic joint disease primarily characterized by destruction of articular cartilage, yet with rare molecular mechanism underlying its development and limited therapeutic targets in clinic. We here to investigate the role of NEAT1 and its molecular basis in OA development. Methods: Rat tissues and chondrocytes with osteoarthritis were used to detect the mRNA level of SMAD7 and miR-424-5p in which the correlation between them was also analyzed; Overexpression and knockdown of miRNA-424-5p were implemented to detect the regulation on SMAD7; The level of inflammatory factors and cell apoptosis of chondrocytes were detected with the opposite treatment on miR-424-5p; The potential interacting lncRNA was identified through online tool and RIP was employed to demonstrate the association between them; The biological coordination between NEAT1 and miR-425-5p in osteoarthritis was explored via the effects on inflammatory factors and cell apoptosis of chondrocytes. Results: Significantly, our results showed that levels of miR-424-5p are negatively correlated to expression of SMAD7 in rat cartilage tissues and chondrocytes, and overexpression of miR-424-5p was demonstrated to down-regulate SMAD7 expression. Additionally, the results also showed that miR-424-5p regulated expression of pro-inflammatory cytokines and apoptosis in chondrocytes via a SMAD7-dependent manner. Morever, the potential interacting lncRNA of miR-424-5p was figured out, and NEAT1 was proved to inversely mediate miR-424-5p expression leading to up-regulation of SMAD7. Further, NEAT1 was also estimated to work concert with miR-424-5p orchestrating expression of pro-inflammatory cytokines and chondrocytes apoptosis to ameliorate development of OA. Conclusions: We here demonstrate that NEAT1 could attenuate OA development via sponging miR-424-5p and thus up-regulating SMAD7 expression. Our data suggest that NEAT1-miR-424-5p-SMAD7 axis might be a potential therapeutic target for OA patients.

Tibial tuberosity advancement in 65 canine stifles

2006 ◽  
Vol 19 (04) ◽  
pp. 219-227 ◽  
Author(s):  
J. M. Miller ◽  
C. P. Ober ◽  
O. I. Lanz ◽  
R. A. Martin ◽  
P. K. Shires ◽  
...  
Keyword(s):  
Cruciate Ligament ◽  
Degenerative Joint Disease ◽  
Activity Level ◽  
Tibial Tuberosity ◽  
Joint Disease ◽  
Patellar Ligament ◽  
Cranial Cruciate Ligament ◽  
The Mean ◽  
Owner Satisfaction

SummaryThe tibial tuberosity advancement (TTA) procedure was developed to treat dogs with cranial cruciate ligament deficient stifles. A retrospective, descriptive study was performed on 57 dogs that underwent unilateral or bilateral TTA. Medical records were reviewed and pre-, postoperative and follow-up radiographs were evaluated for patellar ligament-tibial plateau angle (α), distance of the tibial tuberosity advancement and progression of degenerative joint disease. A questionnaire was sent to all owners to obtain their assessment of the procedural outcome. Sixty-five stifles in 57 dogs received a TTA. Mean age was 5.2 ± 2.5 years while mean weight was 39.7 ± 11.9 kg. Eighteen breeds were represented with Labrador retrievers and mixed breeds predominating. The mean duration of lameness prior to surgery was 6.2 ± 6.7 months, with a median lameness score of 3/4. Fifty-nine percent of cases encountered complications, the majority of which were minor. Major post-operative complications were uncommon but consisted of implant failure, tibial crest displacement and medial meniscal tears. The mean radiographic preoperative angle α was 100°, while the postoperative was 95.5°. Mean osteoarthrosis scores were significantly different between preoperative and follow-up radiographs with 67% of cases showing radiographic progression. Seventy percent of owners responded to the survey with overall outcome considered good to excellent in 90%. Activity level was improved in 90% of responses. TTA subjectively appears to be a useful alternative in the management of cranial cruciate ligament disease. Few severe complications were encountered. Good clinical outcome and owner satisfaction was reported with the procedure in this set of cases.

scholarly journals Dihydromyricetin attenuates inflammation through TLR4/NF-kappaB pathway

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 719-725 ◽  
Author(s):  
Nianshui Jing ◽  
Xinnan Li
Keyword(s):  
Primary Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α ◽  
Cox 2 ◽  
Nf Kappab ◽  
Factor Α ◽  
Oxide Synthase

AbstractMicroglia plays a complex role in neuroinflammation, which has been implicated in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. This study aims to explore the effect and mechanism of Dihydromyricetin (DHM) on lipopolysaccharide (LPS)-induced inflammation in microglial BV-2 cells. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) assay. The pro-inflammatory mediators and cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α); inducible nitric oxide synthase (iNOS); and cyclooxygenase 2 (COX-2) were measured by enzyme-linked immunosorbent assay (ELISA) and/or quantitative real-time PCR (qRT-PCR). The expression of p-p65, p-IκBα, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) were analyzed by western blot. The present study showed that DHM treatment alleviated LPS-induced viability reduction, suppressed the mRNA levels of IL-6, IL‐1β and TNF-α, inhibited the mRNA and protein expression of iNOS and COX-2, and attenuated the activation of NF-кB and TLR4 signaling in a concentration-dependent manner. In conclusion, DHM exerts an anti-inflammatory effect on LPS-induced BV-2 microglial cells, possibly through TRL4/NF-κB signaling pathway.

CircRNA-MSR Regulates LPS-Induced C28/I2 Chondrocyte Injury through miR-643/MAP2K6 Signaling Pathway

Cartilage ◽  
2021 ◽  
pp. 194760352110448
Author(s):  
Zhen Jia ◽  
Qing-Jun Wei
Keyword(s):  
Cell Proliferation ◽  
Degenerative Joint Disease ◽  
Mitogen Activated Protein Kinase ◽  
Joint Disease ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Enzyme Linked Immunosorbent Assay ◽  
Luciferase Reporter Gene ◽  
Rna Fish

Objective Osteoarthritis (OA) is a degenerative joint disease characterized by deterioration of articular cartilage functions. Previous studies have confirmed the role of circular RNAs (circRNAs) in OA, but the role of mechanical stress–related circRNA (circRNA-MSR) in OA is unknown. Design The human chondrocytes C28/I2 were cultured and treated with lipopolysaccharide (LPS) to establish the OA model. The mRNA and protein levels were measured by qRT-PCR or Western blot. Cell viability was analyzed by MTT assay. Flow cytometry was carried out to detect cell apoptosis. The levels of TNF-α, IL-1β, and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). Pull-down assay was conducted to measure circRNA-MSR-related miRNA. Dual-luciferase reporter gene detection was performed to detect the target relationships between miR-643 and circRNA-MSR or Mitogen-activated protein kinase kinase 6 (MAP2K6). The RNA–fluorescence in situ hybridization (RNA-FISH) assay was conducted to verify the localization of circRNA-MSR and miR-643. Results The expressions of circRNA-MSR were upregulated in LPS stimulated C28/I2 cells. Knockdown of circRNA-MSR can inhibit LPS-induced apoptosis, inflammatory response, and extracellular matrix (ECM) degradation, and promote cell C28/I2 cells proliferation. Moreover, circRNA-MSR directly targeted miR-643. RNA-FISH exhibited that circRNA-MSR may act as a competing endogenous RNA (ceRNA) of miR-643. Over-expression of miR-643 could alleviate LPS-induced C28/I2 chondrocyte injury and promote cell proliferation. Besides, miR-643 directly bound to MAP2K6 mRNA. MiR-643 inhibition or MAP2K6 overexpression can reverse the role of circRNA-MSR knockdown on LPS-treated chondrocytes. Conclusion circRNA-MSR can upregulate MAP2K6 by targeting miR-643, thereby inhibiting cell proliferation and promoting apoptosis of C28/I2 cells.

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