PMID- 32869899
OWN - NLM
STAT- MEDLINE
DCOM- 20210709
LR  - 20211204
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 44
IP  - 12
DP  - 2020 Dec
TI  - microRNA-199a counteracts glucocorticoid inhibition of bone marrow mesenchymal 
      stem cell osteogenic differentiation through regulation of Klotho expression in 
      vitro.
PG  - 2532-2540
LID - 10.1002/cbin.11460 [doi]
AB  - Osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) is 
      critically important for mitigation of osteoporosis. Glucocorticoids (GCs) are 
      extensively used for treating chronic inflammation, although long-term exposure 
      to GCs is capable of triggering osteoporosis. microRNAs (miRNAs) have been 
      reported to play a critical role in bone diseases. In the present study, we 
      treated BMSCs with dexamethasone (DEX) during OD to stimulate GC-mediated 
      osteoporosis. Microarray and quantitative polymerase chain reaction (Q-PCR) 
      assays demonstrated that miR-199a was upregulated during OD of BMSCs, while DEX 
      treatment caused a significant reduction in miR-199a. Alkaline phosphatase (ALP) 
      activity, Alizarin red (AR) staining, and Q-PCR were applied to assess the role 
      of miRNA-199a overexpression in DEX-triggered OD inhibition. miR-199a was able to 
      rescue OD and ALP activity, which were inhibited by DEX. Additionally, we 
      observed that ALP, BMP2, COL1A1, and Runx2 were increased after transfection of 
      miRNA-199a mimics. Furthermore, we confirmed that miRNA-199a facilitates OD of 
      BMSCs through direct inhibition of Klotho protein and messenger RNA expression 
      affecting the downstream fibroblast growth factor receptor 
      1/extracellular-signal-regulated kinase and Janus kinase 1/signal transducer and 
      activator of transcription 1 pathways. This study indicates that miR-199a plays a 
      critical role in preventing GC-mediated osteoblast differentiation and may 
      function as a promising miRNA biomarker for osteoporosis.
CI  - (c) 2020 International Federation for Cell Biology.
FAU - Tang, Jinshan
AU  - Tang J
AD  - Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical 
      University, Huai'an, Jiangsu, China.
AD  - Department of Orthopedics, The Second People's Hospital of Huai'an, Huai'an, 
      Jiangsu, China.
FAU - Yu, Huaixi
AU  - Yu H
AD  - Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical 
      University, Huai'an, Jiangsu, China.
AD  - Department of Orthopedics, The Second People's Hospital of Huai'an, Huai'an, 
      Jiangsu, China.
FAU - Wang, Yunqing
AU  - Wang Y
AD  - Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical 
      University, Xuzhou, Jiangsu, China.
FAU - Duan, Gang
AU  - Duan G
AD  - Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical 
      University, Xuzhou, Jiangsu, China.
FAU - Wang, Bin
AU  - Wang B
AD  - Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical 
      University, Xuzhou, Jiangsu, China.
FAU - Li, Wenbo
AU  - Li W
AD  - Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical 
      University, Xuzhou, Jiangsu, China.
FAU - Zhu, Ziqiang
AU  - Zhu Z
AUID- ORCID: 0000-0001-8848-2451
AD  - Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical 
      University, Xuzhou, Jiangsu, China.
LA  - eng
PT  - Journal Article
DEP - 20200910
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Glucocorticoids)
RN  - 0 (MIRN199 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - EC 3.2.1.31 (Klotho Proteins)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/metabolism
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Dexamethasone/adverse effects/pharmacology
MH  - Female
MH  - Glucocorticoids/metabolism/pharmacology
MH  - Glucuronidase/*metabolism
MH  - Klotho Proteins
MH  - Male
MH  - Mesenchymal Stem Cells/cytology/metabolism
MH  - MicroRNAs/*genetics/metabolism
MH  - Osteoblasts/metabolism
MH  - Osteogenesis/drug effects/*genetics
MH  - Osteoporosis/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - GC
OT  - Klotho
OT  - OD
OT  - bone marrow mesenchymal stem cells
OT  - microRNA-199a
EDAT- 2020/09/02 06:00
MHDA- 2021/07/10 06:00
CRDT- 2020/09/02 06:00
PHST- 2020/04/09 00:00 [received]
PHST- 2020/08/11 00:00 [revised]
PHST- 2020/08/30 00:00 [accepted]
PHST- 2020/09/02 06:00 [pubmed]
PHST- 2021/07/10 06:00 [medline]
PHST- 2020/09/02 06:00 [entrez]
AID - 10.1002/cbin.11460 [doi]
PST - ppublish
SO  - Cell Biol Int. 2020 Dec;44(12):2532-2540. doi: 10.1002/cbin.11460. Epub 2020 Sep 
      10.