Chinese Journal of Tissue Engineering Research ›› 2020, Vol. 24 ›› Issue (11): 1641-1646.doi: 10.3969/j.issn.2095-4344.2530

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Effect of miR-455-3p targeting HIPK2 on proliferation and apoptosis of osteoblasts induced by high glucose

Kuang Jiabing1, Shen Wenjuan2, Ma Yonggang3, Xu Hao1, Zhang Keliang1, Shen Bo1, Xu Yanyan1   

  1. 1Department of Orthopedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology; 2Department of Critical Care Medicine, the Second Hospital, University of South China, ; 3Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430030, Hubei Province, China
  • Received:2019-06-27 Revised:2019-07-02 Accepted:2019-08-09 Online:2020-04-18 Published:2020-02-21
  • Contact: Shen Wenjuan, Master, Department of Critical Care Medicine, the Second Hospital, University of South China, Hengyang 421099, Hunan Province, China
  • About author:Kuang Jiabing, Master, Attending physician, Department of Orthopedics, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
  • Supported by:
    the Hubei Provincial Health and Family Planning Commission Project, No. WJ2015MB087

Abstract:

BACKGROUND: Previous studies have shown that various miRNAs play a role in bone formation. miR-335-5p can protect osteoblasts from oxidative stress and protect osteoblasts under induction with ferric ammonium citrate, but the effect of miR-335-5p on osteoblast proliferation and apoptosis in high glucose environments is unknown.

OBJECTIVE: To investigate the effect of miR-455-3p targeting HIPK2 on proliferation and apoptosis of osteoblasts induced by high glucose.

METHODS: Dual luciferase reporter assay was used to verify the targeting of miR-455-3p to HIPK2. MC3T3-E1 cells were induced by high glucose in vitro, and MC3T3-E1 cells were treated as follows: blank group, high glucose group, high glucose+miR-control group, high glucose+miR-455-3p group, high sugar+si-control group, high sugar+si-HIPK2 group, high glucose+miR-455-3p+pcDNA group and high glucose+miR-455-3p+pcDNA-HIPK2 group. The expression of miR-455-3p and HIPK2 mRNA was detected by qRT-PCR, cell viability was detected by MTT assay, apoptosis was detected by flow cytometry, and the expression of HIPK2, p-STAT3 and STAT3 protein was detected by western blot.

RESULTS AND CONCLUSION: HIPK2 was a target gene of miR-455-3p, and miR-455-3p negatively regulated the expression of HIPK2. High glucose treatment inhibited the expression of miR-455-3p and promoted the expression of HIPK2. The over-expression of miR-455-3p or the inhibition of HIPK2 promoted MC3T3-E1 survival and inhibit cell apoptosis after high glucose treatment. The over-expression of HIPK2 partially reversed the survival promotion and apoptosis inhibition of miR-455-3p on osteoblasts induced by high glucose. miR-455-3p inhibited the expression of p-STAT3 in osteoblasts by regulating HIPK2. To conclude, miR-455-3p inhibits the apoptosis and promotes the proliferation of osteoblasts induced by high glucose via down-regulating HIPK2, which may be related to the inhibition of STAT3 signaling pathway.

Key words: miR-455-3p, HIPK2, high glucose, osteoblasts, apoptosis, STAT3 signaling pathway

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