PMID- 31959744
OWN - NLM
STAT- MEDLINE
DCOM- 20210114
LR  - 20210119
IS  - 2041-4889 (Electronic)
VI  - 11
IP  - 1
DP  - 2020 Jan 20
TI  - P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to 
      promote the repair of early steroid-induced osteonecrosis of the femoral head.
PG  - 42
LID - 10.1038/s41419-020-2238-1 [doi]
LID - 42
AB  - Survival and stemness of bone marrow mesenchymal stem cells (BMSCs) in 
      osteonecrotic areas are especially important in the treatment of early 
      steroid-induced osteonecrosis of the femoral head (ONFH). We had previously used 
      BMSCs to repair early steroid-induced ONFH, but the transplanted BMSCs underwent 
      a great deal of stress-induced apoptosis and aging in the oxidative-stress (OS) 
      microenvironment of the femoral-head necrotic area, which limited their efficacy. 
      Our subsequent studies have shown that under OS, massive accumulation of damaged 
      mitochondria in cells is an important factor leading to stress-induced apoptosis 
      and senescence of BMSCs. The main reason for this accumulation is that OS leads 
      to upregulation of protein 53 (P53), which inhibits mitochondrial translocation 
      of Parkin and activation of Parkin's E3 ubiquitin ligase, which decreases the 
      level of mitophagy and leads to failure of cells to effectively remove damaged 
      mitochondria. However, P53 downregulation can effectively reverse this process. 
      Therefore, we upregulated Parkin and downregulated P53 in BMSCs. We found that 
      this significantly enhanced mitophagy in BMSCs, decreased the accumulation of 
      damaged mitochondria in cells, effectively resisted stress-induced BMSCs 
      apoptosis and senescence, and improved the effect of BMSCs transplantation on 
      early steroid-induced ONFH.
FAU - Zhang, Fei
AU  - Zhang F
AD  - Department of Orthopedics, The Affliated Hospital of Guizhou Medical University, 
      Guiyang, Guizhou, 550004, China.
AD  - Guizhou Medical University, Guiyang, Guizhou, 550004, China.
FAU - Peng, Wuxun
AU  - Peng W
AD  - Department of Orthopedics, The Affliated Hospital of Guizhou Medical University, 
      Guiyang, Guizhou, 550004, China. 903463644@qq.com.
AD  - Guizhou Medical University, Guiyang, Guizhou, 550004, China. 903463644@qq.com.
FAU - Zhang, Jian
AU  - Zhang J
AD  - Department of Orthopedics, The Affliated Hospital of Guizhou Medical University, 
      Guiyang, Guizhou, 550004, China.
AD  - Guizhou Medical University, Guiyang, Guizhou, 550004, China.
FAU - Dong, Wentao
AU  - Dong W
AD  - Department of Orthopedics, The Affliated Hospital of Guizhou Medical University, 
      Guiyang, Guizhou, 550004, China.
AD  - Guizhou Medical University, Guiyang, Guizhou, 550004, China.
FAU - Wu, Jianhua
AU  - Wu J
AD  - Department of Orthopedics, The Affliated Hospital of Guizhou Medical University, 
      Guiyang, Guizhou, 550004, China.
AD  - Guizhou Medical University, Guiyang, Guizhou, 550004, China.
FAU - Wang, Tao
AU  - Wang T
AD  - Guizhou Medical University, Guiyang, Guizhou, 550004, China.
FAU - Xie, Zhihong
AU  - Xie Z
AD  - Guizhou Medical University, Guiyang, Guizhou, 550004, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200120
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Steroids)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (parkin protein)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cellular Senescence/genetics
MH  - Disease Models, Animal
MH  - Femur Head Necrosis/chemically induced/genetics/*metabolism/*pathology
MH  - Gene Expression Regulation
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*metabolism/ultrastructure
MH  - Mitochondria/pathology/ultrastructure
MH  - *Mitophagy/genetics
MH  - Models, Biological
MH  - Osteogenesis
MH  - Oxidative Stress/genetics
MH  - Rabbits
MH  - Steroids/*adverse effects
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
MH  - *Wound Healing
PMC - PMC6971291
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/01/22 06:00
MHDA- 2021/01/15 06:00
PMCR- 2020/01/20
CRDT- 2020/01/22 06:00
PHST- 2019/08/19 00:00 [received]
PHST- 2019/12/20 00:00 [accepted]
PHST- 2019/12/20 00:00 [revised]
PHST- 2020/01/22 06:00 [entrez]
PHST- 2020/01/22 06:00 [pubmed]
PHST- 2021/01/15 06:00 [medline]
PHST- 2020/01/20 00:00 [pmc-release]
AID - 10.1038/s41419-020-2238-1 [pii]
AID - 2238 [pii]
AID - 10.1038/s41419-020-2238-1 [doi]
PST - epublish
SO  - Cell Death Dis. 2020 Jan 20;11(1):42. doi: 10.1038/s41419-020-2238-1.