PMID- 32799744
OWN - NLM
STAT- MEDLINE
DCOM- 20210903
LR  - 20211204
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Linking)
VI  - 29
IP  - 20
DP  - 2020 Oct 15
TI  - Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against 
      Compression-Induced Apoptosis in the Degenerative Disc Microenvironment Through 
      Activation of the HIF-1alpha/YAP Signaling Pathway.
PG  - 1309-1319
LID - 10.1089/scd.2020.0061 [doi]
AB  - Stem cell therapy provides an attractive solution for intervertebral disc (IVD) 
      degeneration. However, the degenerative microenvironment, characterized by 
      excessive mechanical loading and hypoxia, remains an obstacle for the 
      long-lasting survival of exogenous transplanted stem cells. Whether and how bone 
      marrow mesenchymal stem cells (BMSCs) adapt to the hostile microenvironment 
      remain unclear. In this study, CoCl(2) and mechanical compression were 
      simultaneously used to simulate the hypoxic and overloaded microenvironment of 
      IVDs in vitro. Compression had a proapoptotic effect through activation of the 
      mitochondrial apoptotic pathway, while hypoxia exerted a prosurvival effect 
      counteracting compression-induced apoptosis. Inhibiting the transcriptional 
      activity of hypoxia inducible factor 1 subunit alpha (HIF-1alpha) by chetomin 
      reversed the antiapoptotic effect of hypoxia. Furthermore, HIF-1alpha promoted 
      dephosphorylation and activation of yes-associated protein (YAP) in hypoxic 
      conditions. Conversely, both YAP inhibition and increased cell apoptosis were 
      observed after inhibition through chetomin or YAP inhibitor verteporfin. 
      Immunofluorescence staining and coimmunoprecipitation assays revealed that YAP 
      could interact directly with HIF-1alpha and colocalize in the nucleus. Taken 
      together, our results demonstrated that hypoxia protected BMSCs against 
      compression-induced apoptosis in the degenerative disc microenvironment through 
      activation of the HIF-1alpha/YAP signaling pathway. Thus, regulation of HIF-1alpha/YAP 
      signaling might provide novel insights for promoting long-lasting BMSC survival 
      and optimizing stem cell therapy for IVD degeneration.
FAU - Wang, Zhe
AU  - Wang Z
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Cui, Min
AU  - Cui M
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Qu, Yanji
AU  - Qu Y
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, China.
FAU - He, Ruijun
AU  - He R
AD  - Department of Developmental Biology, Washington University School of Medicine, 
      St. Louis, Missouri, USA.
FAU - Wu, Wei
AU  - Wu W
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Lin, Hui
AU  - Lin H
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Shao, Zengwu
AU  - Shao Z
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200909
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yap1 protein, rat)
RN  - 3G0H8C9362 (Cobalt)
RN  - EVS87XF13W (cobaltous chloride)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cell Hypoxia/drug effects
MH  - Cell Survival/drug effects
MH  - *Cellular Microenvironment/drug effects
MH  - Cobalt/pharmacology
MH  - *Cytoprotection/drug effects
MH  - Female
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Intervertebral Disc Degeneration/*pathology
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Mesenchymal Stem Cells/*cytology/drug effects
MH  - Models, Biological
MH  - Rats, Sprague-Dawley
MH  - *Signal Transduction/drug effects
MH  - *Stress, Mechanical
MH  - YAP-Signaling Proteins
OTO - NOTNLM
OT  - HIF-1alpha
OT  - YAP
OT  - apoptosis
OT  - bone marrow mesenchymal stem cells
OT  - hypoxia
OT  - intervertebral disc degeneration
EDAT- 2020/08/18 06:00
MHDA- 2021/09/04 06:00
CRDT- 2020/08/18 06:00
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2021/09/04 06:00 [medline]
PHST- 2020/08/18 06:00 [entrez]
AID - 10.1089/scd.2020.0061 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2020 Oct 15;29(20):1309-1319. doi: 10.1089/scd.2020.0061. Epub 
      2020 Sep 9.