PMID- 31829736
OWN - NLM
STAT- MEDLINE
DCOM- 20210604
LR  - 20211204
IS  - 2152-4998 (Electronic)
IS  - 2152-4971 (Linking)
VI  - 22
IP  - 1
DP  - 2020 Feb
TI  - The Positive Effect of TET2 on the Osteogenic Differentiation of Human 
      Adipose-Derived Mesenchymal Stem Cells.
PG  - 3-13
LID - 10.1089/cell.2019.0045 [doi]
AB  - This study aims to understand the possible effects of TET2 (ten-eleven 
      translocation 2) on the osteogenic differentiation of human adipose-derived 
      mesenchymal stem cells (ADSCs). The human ADSCs were transfected with TET2 
      siRNAs. The osteogenesis-related genes were detected by quantitative real-time 
      reverse transcription PCR (qRT-PCR), and the osteogenic differentiation was 
      evaluated by alkaline phosphatase (ALP) staining and Alizarin Red staining. TET2 
      and 5-hydroxymethylcytosine (5hmC) expressions were determined by western 
      blotting and immunofluorescence staining. Meanwhile, wild-type (WT) and 
      TET2-deficient (TET2(-/-)) mice were selected to observe the alteration of 
      biological characteristics in vivo. TET2 was significantly upregulated along with 
      the osteogenic differentiation of human ADSCs. Compared with Blank group, TET2 
      siRNA-3 group showed apparent reductions in TET2, 5hmC, and osteogenesis-related 
      genes, as well as decreases in mineralized nodules, ALP activity, and cell growth 
      (all p < 0.05). Besides, Tet2(-/-) mice had shorter femoral length, lower bone 
      mineral density, and reduced bone volume to total volume (BV/TV) ratio relevant 
      to WT mice; and meanwhile, the percentage of TUNEL-positive chondrocytes 
      increased significantly with the decreased total collagen-positive area, and the 
      distance between two markers of calcein narrowed with declined bone formation 
      rate (BFR) and mineral apposition rate (all p < 0.05). Furthermore, Toluidine 
      Blue staining presented the appreciable decrease of BFR/bone surface (BS) ratio, 
      BFR/BV ratio, osteoblast number over bone perimeter (N.Oc/B.Pm), and osteoblast 
      surface (Ob.S)/BS in Tet2(-/-) mice (all p < 0.05). Taken together, TET2 
      upregulation was observed during the osteogenic differentiation of ADSCs, whereas 
      TET2 inhibition may lead to reductions of osteogenesis-related genes and 
      downexpression of 5hmC, which eventually plays a negative role in osteoporosis.
FAU - Feng, Li
AU  - Feng L
AD  - Department of Traumatic Orthopedics, Jining No. 1 People's Hospital, Jining, 
      China.
FAU - Zhou, Jing
AU  - Zhou J
AD  - Department of Gynecology, Jining No. 1 People's Hospital, Jining, China.
FAU - Xia, Bo
AU  - Xia B
AD  - Department of Traumatic Orthopedics, Jining No. 1 People's Hospital, Jining, 
      China.
FAU - Tian, Bao-Fang
AU  - Tian BF
AD  - Department of Traumatic Orthopedics, Jining No. 1 People's Hospital, Jining, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20191212
PL  - United States
TA  - Cell Reprogram
JT  - Cellular reprogramming
JID - 101528176
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 6R795CQT4H (5-Methylcytosine)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.- (TET1 protein, human)
RN  - EC 1.13.11.- (Dioxygenases)
RN  - EC 1.13.11.- (TET2 protein, human)
RN  - EC 1.13.11.- (Tet2 protein, mouse)
SB  - IM
MH  - 5-Methylcytosine/*metabolism
MH  - Adipose Tissue
MH  - Adult
MH  - Animals
MH  - Bone and Bones/cytology
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Dioxygenases
MH  - Female
MH  - Gene Silencing
MH  - Humans
MH  - Mesenchymal Stem Cells/*cytology
MH  - Mice
MH  - Mice, Knockout
MH  - Mixed Function Oxygenases/metabolism
MH  - Osteoblasts/*cytology
MH  - Osteogenesis/genetics
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - RNA, Small Interfering/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Transfection
MH  - Up-Regulation
OTO - NOTNLM
OT  - ADSCs
OT  - TET2
OT  - osteogenic differentiation
OT  - osteoporosis
EDAT- 2019/12/13 06:00
MHDA- 2021/06/05 06:00
CRDT- 2019/12/13 06:00
PHST- 2019/12/13 06:00 [pubmed]
PHST- 2021/06/05 06:00 [medline]
PHST- 2019/12/13 06:00 [entrez]
AID - 10.1089/cell.2019.0045 [doi]
PST - ppublish
SO  - Cell Reprogram. 2020 Feb;22(1):3-13. doi: 10.1089/cell.2019.0045. Epub 2019 Dec 
      12.