PMID- 33902432
OWN - NLM
STAT- MEDLINE
DCOM- 20211123
LR  - 20211123
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 27
IP  - 1
DP  - 2021 Apr 26
TI  - MiR-27a-3p promotes the osteogenic differentiation by activating CRY2/ERK1/2 
      axis.
PG  - 43
LID - 10.1186/s10020-021-00303-5 [doi]
LID - 43
AB  - BACKGROUND: Osteoporosis seriously disturbs the life of people. Meanwhile, 
      inhibition or weakening of osteogenic differentiation is one of the important 
      factors in the pathogenesis of osteoporosis. It was reported that miR-27a-3p 
      reduced the symptoms of osteoporosis. However, the mechanism by which miR-27a-3p 
      in osteogenic differentiation remains largely unknown. METHODS: To induce the 
      osteogenic differentiation in MC3T3-E1 cells, cells were treated with osteogenic 
      induction medium (OIM). RT-qPCR was used to evaluate the mRNA expression of 
      miR-27a-3p and CRY2 in cells. The protein levels of CRY2, Runt-related 
      transcription factor 2 (Runx2), osteopontin (OPN), osteocalcin (OCN) and the 
      phosphorylation level of extracellular regulated protein kinases (ERK) 1/2 in 
      MC3T3-E1 cells were evaluated by western blotting. Meanwhile, calcium nodules and 
      ALP activity were tested by alizarin red staining and ALP kit, respectively. 
      Luciferase reporter gene assay was used to analyze the correlation between CRY2 
      and miR-27a-3p. RESULTS: The expression of miR-27a-3p and the phosphorylation 
      level of ERK1/2 were increased by OIM in MC3T3-E1 cells, while CRY2 expression 
      was decreased. In addition, OIM-induced increase of calcified nodules, ALP 
      content and osteogenesis-related protein expression was significantly reversed by 
      downregulation of miR-27a-3p and overexpression of CRY2. In addition, miR-27a-3p 
      directly targeted CRY2 and negatively regulated CRY2. Meanwhile, the inhibitory 
      effect of miR-27a-3p inhibitor on osteogenic differentiation was reversed by 
      knockdown of CRY2 or using honokiol (ERK1/2 signal activator). Furthermore, 
      miR-27a-3p significantly inhibited the apoptosis of MC3T3-E1 cells treated by 
      OIM. Taken together, miR-27a-3p/CRY2/ERK axis plays an important role in 
      osteoblast differentiation. CONCLUSIONS: MiR-27a-3p promoted osteoblast 
      differentiation via mediation of CRY2/ERK1/2 axis. Thereby, miR-27a-3p might 
      serve as a new target for the treatment of osteoporosis.
FAU - Ren, Li-Rong
AU  - Ren LR
AD  - Department of Spine Surgery, The First Affiliated Hospital of Dali University, 
      No.32, Jiashibo Avenue, Dali, 671000, Yunnan Province, People's Republic of 
      China.
FAU - Yao, Ru-Bin
AU  - Yao RB
AD  - Department of Spine Surgery, The First Affiliated Hospital of Dali University, 
      No.32, Jiashibo Avenue, Dali, 671000, Yunnan Province, People's Republic of 
      China.
FAU - Wang, Shi-Yong
AU  - Wang SY
AD  - Department of Spine Surgery, The First Affiliated Hospital of Dali University, 
      No.32, Jiashibo Avenue, Dali, 671000, Yunnan Province, People's Republic of 
      China.
FAU - Gong, Xiang-Dong
AU  - Gong XD
AD  - Department of Spine Surgery, The First Affiliated Hospital of Dali University, 
      No.32, Jiashibo Avenue, Dali, 671000, Yunnan Province, People's Republic of 
      China.
FAU - Xu, Ji-Tao
AU  - Xu JT
AD  - Department of Spine Surgery, The First Affiliated Hospital of Dali University, 
      No.32, Jiashibo Avenue, Dali, 671000, Yunnan Province, People's Republic of 
      China.
FAU - Yang, Kai-Shun
AU  - Yang KS
AUID- ORCID: 0000-0002-6828-3719
AD  - Department of Spine Surgery, The First Affiliated Hospital of Dali University, 
      No.32, Jiashibo Avenue, Dali, 671000, Yunnan Province, People's Republic of 
      China. yangkais47@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210426
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Cry2 protein, mouse)
RN  - 0 (Cryptochromes)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn27 microRNA, mouse)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Autophagy/genetics
MH  - Cell Differentiation/genetics
MH  - Cell Line
MH  - Cryptochromes/genetics/metabolism
MH  - Down-Regulation
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - *MicroRNAs
MH  - Osteoblasts/*cytology
MH  - Osteogenesis/*genetics
PMC - PMC8077963
OTO - NOTNLM
OT  - ERK1/2 pathway
OT  - Osteogenic differentiation
OT  - Osteoporosis
OT  - miR-27a-3p
COIS- The authors declare that they have no conflict of interest.
EDAT- 2021/04/28 06:00
MHDA- 2021/11/24 06:00
PMCR- 2021/04/26
CRDT- 2021/04/27 05:36
PHST- 2020/11/09 00:00 [received]
PHST- 2021/04/14 00:00 [accepted]
PHST- 2021/04/27 05:36 [entrez]
PHST- 2021/04/28 06:00 [pubmed]
PHST- 2021/11/24 06:00 [medline]
PHST- 2021/04/26 00:00 [pmc-release]
AID - 10.1186/s10020-021-00303-5 [pii]
AID - 303 [pii]
AID - 10.1186/s10020-021-00303-5 [doi]
PST - epublish
SO  - Mol Med. 2021 Apr 26;27(1):43. doi: 10.1186/s10020-021-00303-5.