PMID- 32894532
OWN - NLM
STAT- MEDLINE
DCOM- 20210504
LR  - 20231213
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 24
IP  - 16
DP  - 2020 Aug
TI  - MiR-145 targeting BNIP3 reduces apoptosis of chondrocytes in osteoarthritis 
      through Notch signaling pathway.
PG  - 8263-8272
LID - 22622 [pii]
LID - 10.26355/eurrev_202008_22622 [doi]
AB  - OBJECTIVE: The purpose of this study was to explore the effect of micro 
      ribonucleic acid (miR)-145 on the apoptosis of chondrocytes in osteoarthritis 
      (OA), and to research the association between its targeting on B-cell lymphoma-2 
      (Bcl-2)/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and Notch signaling 
      pathway and chondrocyte apoptosis. MATERIALS AND METHODS: The mouse model of OA 
      was established via surgery, and chondrocytes were isolated and cultured in 
      vitro. Then, the chondrocytes were transfected with miR-145 inhibitor, miR-145 
      mimics, miR-negative control (NC), BNIP3-siRNA and BNIP3-vector, respectively, 
      with those normally cultured as the control. After that, the expression levels of 
      miR-145 and BNIP3 in cells were detected via quantitative Reverse 
      Transcription-Polymerase Chain Reaction (qRT-PCR), the apoptosis rate was 
      detected via flow cytometry, and the apoptosis level was detected using terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. 
      Moreover, the target gene sequences were predicted and compared using the 
      software, and the BNIP3 Luciferase reporter vectors containing predicted target 
      sites for miR-145 were constructed. Finally, the protein expressions of BNIP3, 
      Notch1, and P21 were determined through Western blotting. RESULTS: The results of 
      qRT-PCR showed that in OA chondrocytes, the expression of miR-145 was lower than 
      that in normal chondrocytes (p<0.05), while the mRNA and protein expressions of 
      BNIP3 were higher than those in normal chondrocytes (p<0.05). According to flow 
      cytometry, the apoptosis rate was (4.4+/-0.6)% in normal cartilage tissues and 
      (29.2+/-2.1)% in OA cartilage tissues. Overexpression of miR-145 significantly 
      reduced chondrocyte apoptosis (p<0.05), while overexpression of BNIP3 markedly 
      increased chondrocyte apoptosis (p<0.05). In addition, the Luciferase reporter 
      system showed that miR-145 mimics evidently inhibited BNIP3 (p<0.05) and 
      suppressed the Notch signaling pathway (p<0.05), while BNIP3 enhanced the 
      expression of Notch signaling pathway (p<0.05). CONCLUSIONS: MiR-145 can reduce 
      OA-induced chondrocyte apoptosis through targeted inhibition on BNIP3 and 
      regulation on Notch signaling pathway.
FAU - Wang, W-F
AU  - Wang WF
AD  - Department of Orthopedic Surgery, Liaocheng People's Hospital, Liaocheng, China. 
      2894173774@qq.com.
FAU - Liu, S-Y
AU  - Liu SY
FAU - Qi, Z-F
AU  - Qi ZF
FAU - Lv, Z-H
AU  - Lv ZH
FAU - Ding, H-R
AU  - Ding HR
FAU - Zhou, W-J
AU  - Zhou WJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (BNip3 protein, mouse)
RN  - 0 (MIRN145a microRNA, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Receptors, Notch)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cells, Cultured
MH  - Chondrocytes/*metabolism/pathology
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - MicroRNAs/*metabolism
MH  - Mitochondrial Proteins/*metabolism
MH  - Osteoarthritis/*metabolism/pathology
MH  - Receptors, Notch/*metabolism
MH  - Signal Transduction
EDAT- 2020/09/08 06:00
MHDA- 2021/05/05 06:00
CRDT- 2020/09/07 12:13
PHST- 2020/09/07 12:13 [entrez]
PHST- 2020/09/08 06:00 [pubmed]
PHST- 2021/05/05 06:00 [medline]
AID - 22622 [pii]
AID - 10.26355/eurrev_202008_22622 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2020 Aug;24(16):8263-8272. doi: 
      10.26355/eurrev_202008_22622.