PMID- 32903671
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220416
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 8
DP  - 2020
TI  - LncRNA H19 Regulates BMP2-Induced Hypertrophic Differentiation of Mesenchymal 
      Stem Cells by Promoting Runx2 Phosphorylation.
PG  - 580
LID - 10.3389/fcell.2020.00580 [doi]
LID - 580
AB  - OBJECTIVES: Bone morphogenetic protein 2 (BMP2) triggers hypertrophic 
      differentiation after chondrogenic differentiation of mesenchymal stem cells 
      (MSCs), which blocked the further application of BMP2-mediated cartilage tissue 
      engineering. Here, we investigated the underlying mechanisms of BMP2-mediated 
      hypertrophic differentiation of MSCs. MATERIALS AND METHODS: In vitro and in vivo 
      chondrogenic differentiation models of MSCs were constructed. The expression of 
      H19 in mouse limb was detected by fluorescence in situ hybridization (FISH) 
      analysis. Transgenes BMP2, H19 silencing, and overexpression were expressed by 
      adenoviral vectors. Gene expression was determined by reverse transcription and 
      quantitative real-time PCR (RT-qPCR), Western blot, and immunohistochemistry. 
      Correlations between H19 expressions and other parameters were calculated with 
      Spearman's correlation coefficients. The combination of H19 and Runx2 was 
      identified by RNA immunoprecipitation (RIP) analysis. RESULTS: We identified that 
      H19 expression level was highest in proliferative zone and decreased gradually 
      from prehypertrophic zone to hypertrophic zone in mouse limbs. With the 
      stimulation of BMP2, the highest expression level of H19 was followed after the 
      peak expression level of Sox9; meanwhile, H19 expression levels were positively 
      correlated with chondrogenic differentiation markers, especially in the late 
      stage of BMP2 stimulation, and negatively correlated with hypertrophic 
      differentiation markers. Our further experiments found that silencing H19 
      promoted BMP2-triggered hypertrophic differentiation through in vitro and in vivo 
      tests, which indicated the essential role of H19 for maintaining the phenotype of 
      BMP2-induced chondrocytes. In mechanism, we characterized that H19 regulated 
      BMP2-mediated hypertrophic differentiation of MSCs by promoting the 
      phosphorylation of Runx2. CONCLUSION: These findings suggested that H19 regulates 
      BMP2-induced hypertrophic differentiation of MSCs by promoting the 
      phosphorylation of Runx2.
CI  - Copyright (c) 2020 Dai, Xiao, Zhao, Chen, Liao and Huang.
FAU - Dai, Guangming
AU  - Dai G
AD  - Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China.
FAU - Xiao, Haozhuo
AU  - Xiao H
AD  - Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China.
FAU - Zhao, Chen
AU  - Zhao C
AD  - Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China.
FAU - Chen, Hong
AU  - Chen H
AD  - Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China.
FAU - Liao, Junyi
AU  - Liao J
AD  - Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China.
FAU - Huang, Wei
AU  - Huang W
AD  - Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China.
LA  - eng
PT  - Journal Article
DEP - 20200729
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC7438821
OTO - NOTNLM
OT  - BMP2
OT  - MSCs
OT  - cartilage tissue engineering
OT  - hypertrophic differentiation
OT  - lncRNA H19
EDAT- 2020/09/10 06:00
MHDA- 2020/09/10 06:01
PMCR- 2020/01/01
CRDT- 2020/09/09 17:56
PHST- 2020/02/11 00:00 [received]
PHST- 2020/06/15 00:00 [accepted]
PHST- 2020/09/09 17:56 [entrez]
PHST- 2020/09/10 06:00 [pubmed]
PHST- 2020/09/10 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2020.00580 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2020 Jul 29;8:580. doi: 10.3389/fcell.2020.00580. 
      eCollection 2020.