›› 2019, Vol. 39 ›› Issue (8): 861-.doi: 10.3969/j.issn.1674-8115.2019.08.009

• Original article (Basic research) • Previous Articles     Next Articles

Inhibition of gastrin on catabolism of rat chondrocytes inducedinterleukin-1β

LI Ying-ying1, LUO Ya-ping2, FU Guo-hui1, 2, CHEN Shi-hui1   

  1. 1. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Pathology Center, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China; 2. Pathology Center, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
  • Online:2019-08-28 Published:2019-09-23
  • Supported by:
    Shanghai Natural Science Foundation,18ZR1421800

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 determinedMTT 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 s 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 detectedreal-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 s of MMP3 and MMP13 genes were significantly downregulatedgastrin. Meanwhile, the 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 ERKactivating its receptor CCKBR, thereby inhibiting the activity of P65 in NF-κB pathway, antagonizing the chondrocyte catabolic activity inducedIL-1β.Accordingly, gastrin may possess the potentials of cartilage matrix protection via inhibiting mRNA s of MMP3 and MMP13 and catabolism in rat chondrocytes.

Key words: gastrin, chondrocyte, catabolism, molecular mechanism

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