DAla2GIP antagonizes H2O2-induced chondrocyte apoptosis and inflammatory factor secretion

• Published in: Bone (New York, N.Y.) Vol. 127; pp. 656 - 663
• Main Authors: Wang, Yuze, Xiang, Chuan, Sun, Xiaojuan, Wu, Song, Lv, Jia, Li, Pengcui, Wei, Xiaochun, Wei, Lei
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2019
• Subjects: Chondrocyte apoptosis; Inflammatory factor; Non-invasive calcium detection; Osteoarthritis (OA); PI3K/Akt/NF-κB pathway; Osteoarthritis (OA); Chondrocyte apoptosis; PI3K/Akt/NF-κB pathway; Non-invasive calcium detection; Inflammatory factor
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2019.05.026

To investigate the protective effects of DAla2GIP against the apoptosis and inflammatory factor secretion in H2O2-induced chondrocyte, and explore the possible mechanisms of DAla2GIP underlying its protection. The chondrocytes were divided into the following four groups: Control, 300 μM H2O2, 100 pM DAla2GIP and 300 μM H2O2 + 100 pM DAla2GIP. The apoptosis of chondrocyte was measured by using mitochondrial membrane potential assay kit (JC-1) and TUNEL assay, the inflammatory factor secretion were assessed by ELISA assay, and the cellular and molecular mechanisms of DAla2GIP protection were investigated by using Real time-PCR, flow cytometry, Non- invasive calcium detection and western blotting techniques. (1) DAPla2GIP prevents apoptosis of chondrocyte induced by H2O2. (2) DAla2GIP alleviated the inflammation of chondrocyte induced by H2O2. (3) DAla2GIP prevents chondrocyte apoptosis by inhibiting calcium influx of chondrocyte and regulating expression of Bcl-2 and Caspase-3induced by H2O2. (4) DAla2GIP inhibited the H2O2 mediated inflammation by up- regulating the expressions of Sox9 and Col2a1 and inhibiting PI3K/Akt/NF-κB pathway. Our experimental results revealed that DAla2GIP prevents chondrocyte apoptosis by inhibiting calcium influx of chondrocyte and induced regulating expression of Bcl-2 and Casp ase-3by H2O2. Further, molecular biology experiments confirmed that DAla2GIP inhibited the H2O2 mediated inflammation vis up-regulating the expressions of Sox9 and Col2a1 and inhibiting PI3K/Akt/NF-κB pathway. The results demonstrate that DAla2GIP has protective properties in H2O2-induced chondrocyte injury, this finding shows that novel GIP analogues have the potential as a novel therapeutic for osteoarthritis patients. •Chondrocyte apoptosis and secretion of inflammatory factors were induced by H2O2.•DAla2GIP prevents chondrocyte apoptosis by regulating expression of Bcl-2 and Caspase-3 and inhibiting calcium influx of chondrocyte induced by H2O2.•DAla2GIP inhibited the H2O2 mediated inflammation vis up-regulating the expressions of Sox9 and Col2a1 and inhibiting PI3K/Akt/NF-κB pathway.•DAla2GIP has protective properties on in H2O2-induced chondrocyte injury.