| Title |
Pioglitazone inhibits advanced glycation end product-induced matrix metalloproteinases and apoptosis by suppressing the activation of MAPK and NF-κB
|
|---|---|
| Published in |
Apoptosis, August 2016
|
| DOI | 10.1007/s10495-016-1280-z |
| Pubmed ID | |
| Authors |
Hai-Bin Zhang, Ying Zhang, Cheng Chen, Yu-Qing Li, Chi Ma, Zhao-Jun Wang |
| Abstract |
Apoptosis and degeneration coming mainly from chondrocytes are important mechanisms in the onset and progression of osteoarthritis. Specifically, advanced glycation end products (AGEs) play an important role in the pathogenesis of osteoarthritis. Pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist has a protective effect on cartilage. This study aims to evaluate the effect of pioglitazone on AGEs-induced chondrocyte apoptosis and degeneration and their underlying mechanism. The in vitro study shows that AGEs induce cleavage of caspase-3 and PARP, up-regulate MMP-13 expression, enhance chondrocyte apoptosis and down-regulate PPARγ expression in human primary chondrocytes, which is reversed by pioglitazone. Furthermore, AGEs activate phosphorylation of Erk, JNK, and p38, and pioglitazone reverses AGEs-induced phosphorylation of Erk and p38. AGEs-induced degradation of IκBα and translocation of nuclear NF-κB p65 is reversed by pioglitazone. Pretreatment of chondrocytes with SB202190 (p38 inhibitor), SP600125 (JNK inhibitor) and BAY-11-7082 (NF-κB inhibitor) inhibit AGEs-induced apoptosis and degeneration. In vivo experiments suggest that pioglitazone reverses AGEs-induced cartilage degeneration and apoptosis in a mouse model, as demonstrated by HE and Safranin O staining, immunohistochemical analyses of Type II collagen (Col II), metalloproteinases (MMPs) and caspase-3. These findings suggest that pioglitazone, a PPARγ agonist, inhibits AGEs-induced chondrocytes apoptosis and degeneration via suppressing the activation of MAPK and NF-κB. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Other | 5 | 21% |
| Student > Master | 5 | 21% |
| Researcher | 3 | 13% |
| Student > Postgraduate | 2 | 8% |
| Student > Ph. D. Student | 1 | 4% |
| Other | 3 | 13% |
| Unknown | 5 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 33% |
| Agricultural and Biological Sciences | 4 | 17% |
| Biochemistry, Genetics and Molecular Biology | 3 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 8% |
| Business, Management and Accounting | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 5 | 21% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 September 2016.
All research outputs
#20,338,537
of 22,884,315 outputs
Outputs from Apoptosis
#634
of 808 outputs
Outputs of similar age
#311,307
of 355,872 outputs
Outputs of similar age from Apoptosis
#15
of 24 outputs
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So far Altmetric has tracked 808 research outputs from this source. They receive a mean Attention Score of 3.6. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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