The expression of p-ATF2 involved in the chondeocytes apoptosis of an endemic osteoarthritis, Kashin-Beck disease

Jing Han,Jiangtao Liu,Xiong Guo,Mikko J Lammi,Peng Xu,Wuhong Tan,Weizhuo Wang,Feng Zhang

doi:10.1186/1471-2474-14-209

Abstract

BackgroundThe purpose of the study was to understand the function and expression of ATF2 by JNK and p38 signal pathways in the chondrocytes apoptosis of articular cartilage of the Kashin-Beck disease (KBD).MethodsThe changes of ATF2, JNK and p38 mRNAs and proteins were investigated between cartilage and chondrocyte as well as KBD and normal. JNK and p38 inhibitors were used as treatments to prevent apoptosis in chondrocytes from KBD patients.ResultsIt was found that the protein levels of p-p38, p-JNK, ATF2 and p-ATF2 increased in KBD human cartilage which is in line with the higher mRNA levels of p38, JNK and ATF2 as compared both with normal cartilage and KBD chondrocytes. In addition, p-ATF2 was only detected in KBD cartilage. Furthermore, JNK inhibitor was more effective than p38 inhibitor in preventing chondrocyte apoptosis at equal concentrations of 10 μM.ConclusionThese findings indicated the expression of p-ATF2 by JNK and p38 signal pathways involved in the chondrocyte apoptosis in cartilage with KBD.

Highlights

The purpose of the study was to understand the function and expression of Activating transcription factor 2 (ATF2) by Jun N-terminal kinase (JNK) and p38 signal pathways in the chondrocytes apoptosis of articular cartilage of the Kashin-Beck disease (KBD)
We performed a quantitative RT-PCR analysis to compare the levels of ATF2, JNK and p38 in KBD cartilage and those in cultured KBD chondrocytes from the same donors
It could be observed that the expression levels of JNK and ATF2 mRNAs were about 3.2-fold (p < 0.01) and 2.7-fold (p < 0.05) higher in cartilage samples than in chondrocytes, while p38 levels remained stable with 1.3-fold in cartilage compare with chondrocytes (Figure 2)

Summary

Introduction

The purpose of the study was to understand the function and expression of ATF2 by JNK and p38 signal pathways in the chondrocytes apoptosis of articular cartilage of the Kashin-Beck disease (KBD). Kashin-Beck disease (KBD) is a chronic, endemic osteoarthropathy which occurs mainly in regions from the northeast China to Sichuan-Tibet Plateau, Russia and North Korea [1]. The KBD manifests cartilage specific pathological changes and chondrocytes apoptosis in vivo It affects mainly the developing hyaline cartilage, causing apoptosis and necrosis of chondrocytes in the epiphyseal, c-Jun N-terminal kinase (JNK) and p38 protein kinase pathways are two major pathways of mitogen-activated protein kinase (MAPK) signal transduction [16], which play important roles in the stimulation of apoptotic signaling as well as inflammatory diseases [17,18,19]. Inflammation may be both a primary event in KBD and/or a secondary event in the disease for the observed biochemical changes with the cartilage, such as the higher expression of TNF-α, VEGF, TGF-β and IL-1 [20,21]

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