PMID- 31663655
OWN - NLM
STAT- MEDLINE
DCOM- 20200929
LR  - 20200929
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 44
IP  - 2
DP  - 2020 Feb
TI  - PTEN promotes intervertebral disc degeneration by regulating nucleus pulposus 
      cell behaviors.
PG  - 583-592
LID - 10.1002/cbin.11258 [doi]
AB  - Intervertebral disc degeneration (IDD) is induced by multiple factors including 
      increased apoptosis, decreased survival, and reduced extracellular matrix (ECM) 
      synthesis in the nucleus pulposus (NP) cells. The tumor suppressor phosphatase 
      and tensin homolog deleted from chromosome 10 (PTEN) is the only known lipid 
      phosphatase counteracting the PI3K/AKT pathway. Loss of PTEN leads to activated 
      PI3K/AKT signaling, which plays a key role in a variety of cancers. However, the 
      role of PTEN/PI3K/AKT signaling nexus in IDD remains unknown. Here, we report 
      that PTEN is overexpressed in degenerative NP, which correlates with inactivated 
      AKT. Using the PTEN knockdown approach by lentivirus-mediated short interfering 
      RNA gene transfer technique, we report that PTEN decreases survival but induces 
      apoptosis and senescence of NP cells. PTEN also inhibits expression and 
      production of ECM components including collagen II, aggrecan, and proteoglycan. 
      Furthermore, PTEN modulates the expression of ECM regulatory molecules SOX-9 and 
      matrix metalloproteinase-3 (MMP-3). Using small-molecule AKT inhibitor GDC-0068, 
      we confirm that PTEN regulates NP cell behaviors through its direct targeting of 
      PI3K/AKT. These findings demonstrate for the first time that PTEN/PI3K/AKT 
      signaling axis plays an important role in the pathogenesis of IDD. Targeting PTEN 
      using gene therapy may represent a promising therapeutic approach against disc 
      degenerative diseases.
CI  - (c) 2019 International Federation for Cell Biology.
FAU - Xi, Yongming
AU  - Xi Y
AD  - Department of Orthopaedics, Affiliated Hospital of Qingdao University Medical 
      College, Qingdao, 266000, China.
FAU - Ma, Jinfeng
AU  - Ma J
AD  - Department of Orthopaedics, Affiliated Hospital of Qingdao University Medical 
      College, Qingdao, 266000, China.
FAU - Chen, Yan
AU  - Chen Y
AD  - Division in Signaling Biology, Research Institute, Princess Margaret Cancer 
      Center, University Health Network, Toronto, M5G 1L7, Canada.
LA  - eng
GR  - 81470104/National Natural Science Foundation of China/
GR  - NSFC/National Natural Science Foundation of China/
GR  - Taishan Scholars Program, China/
PT  - Journal Article
DEP - 20191112
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Biomarkers)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Apoptosis
MH  - Biomarkers/metabolism
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Intervertebral Disc Degeneration/etiology/metabolism/*pathology
MH  - Male
MH  - Middle Aged
MH  - Nucleus Pulposus/metabolism/*pathology
MH  - PTEN Phosphohydrolase/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Signal Transduction
MH  - Young Adult
OTO - NOTNLM
OT  - AKT
OT  - PTEN
OT  - intervertebral disc degeneration
OT  - nucleus pulposus
EDAT- 2019/10/31 06:00
MHDA- 2020/09/30 06:00
CRDT- 2019/10/31 06:00
PHST- 2019/06/26 00:00 [received]
PHST- 2019/10/26 00:00 [accepted]
PHST- 2019/10/31 06:00 [pubmed]
PHST- 2020/09/30 06:00 [medline]
PHST- 2019/10/31 06:00 [entrez]
AID - 10.1002/cbin.11258 [doi]
PST - ppublish
SO  - Cell Biol Int. 2020 Feb;44(2):583-592. doi: 10.1002/cbin.11258. Epub 2019 Nov 12.