Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (13): 2094-2100.doi: 10.3969/j.issn.2095-4344.1692

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Effects of prostaglandin E2 in the co-culture of anterior cruciate ligament fibroblasts and synoviocytes

Cai Linyi, Pi Caixia, Xie Jing   

  1. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Revised:2018-11-02 Online:2019-05-08 Published:2019-05-08
  • Contact: Xie Jing, MD, Associate professor, Master’s supervisor, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
  • About author:Cai Linyi, Master candidate, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Supported by:

    the National Natural Science Foundation of China (Youth Program), No. 81600840

Abstract:

BACKGROUND: Co-culture of synoviocytes with anterior cruciate ligament fibroblasts can optimize the simulation of articular microenvironment after ligament injuries. The serious imbalance between the expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) induced by prostaglandin E2 and other inflammatory factors could certainly indicate the poor self-healing capability of the anterior cruciate ligament. 
OBJECTIVE: To investigate the effects of prostaglandin E2 on cell migration and gene expressions of TIMPs in synoviocytes co-cultured with anterior cruciate ligament fibroblasts. 
METHODS: Human synoviocytes were mono-cultured or co-cultured with anterior cruciate ligament fibroblasts in the Transwell chamber. Then the mono-cultured and co-cultured synoviocytes were treated with prostaglandin E2. Cell migration was assessed by wound healing assay at 24 hours after prostaglandin E2 treatment. Semi-quantitative PCR was done to analyze the gene expressions of TIMPs in synoviocytes. 
RESULTS AND CONCLUSION: (1) Prostaglandin E2 intensely inhibited the cell migration of synoviocytes (P < 0.05), and the inhibitory effect was more significant in the mono-cultured synoviocytes compared with the co-cultured cells (P < 0.05). (2) Gene expressions of TIMPs in the mono-cultured synoviocytes were down-regulated by prostaglandin E2 in a dose-dependent manner (P < 0.05). The inhibitory effect on TIMP-2 and TIMP-4 was time-dependent, while the gene expressions of TIMP-1 and TIMP-3 were up-regulated with the increase of induction time. (3) The variation of TIMPs expression in the co-cultured group was insignificant as compared with that in the mono-cultured group, but the expression level of TIMPs in the co-cultured group was significantly higher than that in the mono-cultured group at each observational time point (P < 0.05). Thus, prostaglandin E2 can suppress cell migration and gene expressions of TIMPs in synoviocytes, and this inhibitory action can be partially reversed by the co-culture via the paracrine effect.

Key words: Prostaglandins, Anterior Cruciate Ligament, Matrix Metalloproteinases, Tissue Engineering

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