scholarly journals Effects of short-term glucocorticoid treatment on changes in cartilage matrix degradation and chondrocyte gene expression induced by mechanical injury and inflammatory cytokines

2011 ◽  
Vol 13 (5) ◽  
pp. R142 ◽  
Author(s):  
Yihong CS Lu ◽  
Christopher H Evans ◽  
Alan J Grodzinsky
Keyword(s):  
Gene Expression ◽  
Inflammatory Cytokines ◽  
Mechanical Injury ◽  
Cartilage Matrix ◽  
Matrix Degradation ◽  
Short Term ◽  
Glucocorticoid Treatment

Abstract 246: Global Analysis of Differentially Expressed Genes in the Aortae of Apoe-deficient Mice Infused with Insulin-like Growth Factor I: Novel Mechanisms of the Anti-atherogenic Effect of IGF-1

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Charlotte E Vaughn ◽  
Jane S Titterington ◽  
Sergiy Sukhanov ◽  
Patrick Delafontaine
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Adhesion Molecules ◽  
Inflammatory Cytokines ◽  
Interferon Γ ◽  
Scavenger Receptors ◽  
Saline Control ◽  
Short Term ◽  
Factor I ◽  
Pro Inflammatory Cytokines

We have previously shown that insulin like growth factor-I (IGF-1) suppresses atherosclerosis progression in ApoE-null mice. To determine mechanisms, ApoE-null mice were chronically infused with IGF-1 (1.5 mg/kg/d, 12 weeks) or saline (control) or treated short-term with IGF-1 (0.4 mg/kg/d, i.p., 1 week) or saline (control). Aortic gene expression of 84 atherosclerosis-related genes-of-interest was analyzed with RT-PCR arrays. Chronic IGF-1 infusion decreased expression levels of pro-apoptotic molecules (Bax, 0.62, BID, 0.26), adhesion molecules (integrin β2, 0.32, integrin α2, 0.28, VCAM-1, 0.43), pro-inflammatory cytokines (TNFα, 0.22, interferon γ, 0.30) and lipoprotein lipase (LPL, an enzyme mediating lipid hydrolysis and tissue uptake of oxidized low density lipoprotein (OxLDL), 0.69). These changes in gene expression correlated with a reduction in atherosclerotic plaque burden (Oil Red-positive aortic valve lesion area, ×000 pixels 2 , IGF-1, 228±13, saline, 268±22), suppression of plaque apoptosis (% apoptotic cells per plaque, IGF-1, 3.4±0.7, saline, 5.8±0.5, P<0.05, TUNEL assay), decrease in plaque TNFα levels (58% reduction vs. saline, P<0.05, immunostaining), and inhibition of serum LPL activity (IGF-1, 1.1±0.2, saline, 3.7±0.4, P<0.05, fluorescence assay). Short-term IGF-1 treatment similarly decreased mRNA levels of Bax (0.68), BID (0.61), integrin β2 (0.62), TNFα (0.50), interferon γ (0.37), LPL (0.42) and also downregulated a group of scavenger receptors (CD36, 0.44, MSR-1, 0.48, MSR-2, 0.52). To further characterize the effect of IGF-1 on LPL we exposed THP-1-derived macrophages to OxLDL (80 ug/ml, 16 h) in the presence or absence of IGF-1. OxLDL increased LPL activity in conditioned media (>5 fold, P<0.01), but pre-treatment with IGF-1 (25 ng/ml, 24 h) reversed LPL upregulation by 52% and suppressed lipid internalization by 88% (P<0.05, Oil Red staining). In summary IGF-1 reduces pro-inflammatory cytokines, pro-apoptotic molecules, adhesion molecules, scavenger receptors, and lipoprotein lipase expression in ApoE-null mice and markedly blunts OxLDL-induced upregulation of LPL and lipid uptake in THP-derived macrophages. These data provide major insights into mechanisms whereby IGF-1 is atheroprotective.

miR-211-5p contributes to chondrocyte differentiation by suppressing Fibulin-4 expression to play a role in osteoarthritis

2019 ◽  
Vol 166 (6) ◽  
pp. 495-502 ◽  
Author(s):  
Hao Liu ◽  
Jun Luo
Keyword(s):  
Inflammatory Cytokines ◽  
Rat Model ◽  
Cartilage Matrix ◽  
Chondrocyte Differentiation ◽  
Matrix Degradation ◽  
Downstream Target ◽  
Promising Target ◽  
Human Disorders ◽  
Pro Inflammatory Cytokines

Abstract MicroRNAs (miRNAs) serve as key regulators in human disorders. Previous research reported that miR-211-5p is down-regulated in osteoarthritis (OA) and that Fibulin-4 inhibits chondrocyte differentiation. However, the role of miR-211-5p in the development of OA has not been clarified, and its downstream target has not been studied. This study aimed to explore the effect of miR-211-5p on chondrocyte differentiation and its influence on OA pathogenesis, as well as the interaction between miR-211-5p and Fibulin-4. In this study, we found that miR-211-5p is significantly down-regulated in articular cartilage tissues in an OA rat model, whereas it is clearly up-regulated during chondrocyte differentiation of ATDC5 cells. Silencing miR-211-5p in ATDC5 cells had an adverse effect on chondrocyte differentiation. Fibulin-4 was identified as a target of miR-211-5p, and miR-211-5p participated in chondrocyte differentiation by negatively regulating Fibulin-4 expression. In the OA rat model, miR-211-5p overexpression facilitated chondrocyte differentiation, along with the reduced pro-inflammatory cytokines level and the level of proteinases responsible for cartilage matrix degradation. In summary, miR-211-5p promotes chondrocyte differentiation by negatively regulating Fibulin-4 expression, and represses the expression of pro-inflammatory cytokines and proteinases responsible for cartilage matrix degradation in OA. miR-211-5p may serve as a promising target for OA treatment.

A critical role for collagen II in cartilage matrix degradation: Collagen II induces pro-inflammatory cytokines and MMPs in primary human chondrocytes

2009 ◽  
Vol 27 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Andreas R. Klatt ◽  
Brigitte Paul-Klausch ◽  
Gabriele Klinger ◽  
Getrud Kühn ◽  
Joerg H. Renno ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Critical Role ◽  
Cartilage Matrix ◽  
Human Chondrocytes ◽  
Matrix Degradation ◽  
Collagen Ii ◽  
Pro Inflammatory Cytokines

scholarly journals Understanding the Action of RARγ Agonists on Human Osteochondroma Explants

2020 ◽  
Vol 21 (8) ◽  
pp. 2686 ◽  
Author(s):  
Sonia A. Garcia ◽  
Hongying Tian ◽  
Yuka Imamura-Kawasawa ◽  
Aidan Fisher ◽  
Ashley Cellini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Human Growth ◽  
Explant Culture ◽  
Cartilage Matrix ◽  
Sequencing Analysis ◽  
Matrix Degradation ◽  
Growth Plate Chondrocytes

Osteochondromas are cartilage-capped growths located proximate to the physis that can cause skeletal deformities, pain, limited motion, and neurovascular impingement. Previous studies have demonstrated retinoic acid receptor gamma (RARγ) agonists to inhibit ectopic endochondral ossification, therefore we hypothesize that RARγ agonists can target on established osteochondromas. The purpose of this study was to examine the action of RARγ agonist in human osteochondromas. Osteochondroma specimens were obtained during surgery, subjected to explant culture and were treated with RARγ agonists or vehicles. Gene expression analysis confirmed the up-regulation of RARγ target genes in the explants treated with NRX 204647 and Palovarotene and revealed strong inhibition of cartilage matrix and increased extracellular matrix proteases gene expression. In addition, immunohistochemical staining for the neoepitope of protease-cleaved aggrecan indicated that RARγ agonist treatment stimulated cartilage matrix degradation. Interestingly, cell survival studies demonstrated that RARγ agonist treatment stimulated cell death. Moreover, RNA sequencing analysis indicates changes in multiple molecular pathways due to RARγ agonists treatment, showing similarly to human growth plate chondrocytes. Together, these findings suggest that RARγ agonist may exert anti-tumor function on osteochondromas by inhibiting matrix synthesis, promoting cartilage matrix degradation and stimulating cell death.

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