Inhibition of gastrin on catabolism of rat chondrocytes induced by interleukin-1β
10.3969/j.issn.1674-8115.2019.08.009
- Author:
Ying-Ying LI
1
Author Information
1. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Pathology Center, Shanghai Jiao Tong University College of Basic Medical Sciences
- Publication Type:Journal Article
- Keywords:
Catabolism;
Chondrocyte;
Gastrin;
Molecular mechanism
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2019;39(8):861-865
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of gastrin on rat chondrocytes treated with interleukin-1β (IL-1β) and underlying mechanism. Methods:Chondrocytes of knee joint of newborn rats were isolated and cultured. The effect of gastrin on cell viability was determined by MTT assay. In addition, after being induced with 10 ng/mL of IL-1β for 2 d, the chondrocytes were treated with 1×10-7 mol/L of gastrin for 3 d. The expressions of chondrocyte catabolic genes, i.e., matrix metalloproteinase 3 (MMP3) and MMP13, and the key proteins in gastrin-related signaling pathway, i.e., cholecystokinin B receptor (CCKBR), extracellular regulated protein kinases (ERK), phospho-ERK (p-ERK) and p65 were detected by real-time PCR and Western blotting, respectively. Results:Gastrin with the concentration of 1×10-7 mol/L had no cytotoxic effects on the viability of chondrocytes. Based on IL-1β induction, the expressions of MMP3 and MMP13 genes were significantly downregulated by gastrin. Meanwhile, the expression of CCKBR in the IL-1β induction group and gastrin treatment groups was higher than that in the normal control group. Gastrin also facilitated the phosphorylation of ERK and resulted in the inhibition of P65. Conclusion:Gastrin increases the phosphorylation level of ERK by activating its receptor CCKBR, thereby inhibiting the activity of P65 in NF-κB pathway, antagonizing the chondrocyte catabolic activity induced by IL-1β. Accordingly, gastrin may possess the potentials of cartilage matrix protection via inhibiting mRNA expressions of MMP3 and MMP13 and catabolism in rat chondrocytes.
