PMID- 33993186
OWN - NLM
STAT- MEDLINE
DCOM- 20211014
LR  - 20211014
IS  - 2041-4889 (Electronic)
VI  - 12
IP  - 5
DP  - 2021 May 15
TI  - Beraprost ameliorates postmenopausal osteoporosis by regulating Nedd4-induced 
      Runx2 ubiquitination.
PG  - 497
LID - 10.1038/s41419-021-03784-8 [doi]
LID - 497
AB  - Bone health requires adequate bone mass, which is maintained by a critical 
      balance between bone resorption and formation. In our study, we identified 
      beraprost as a pivotal regulator of bone formation and resorption. The 
      administration of beraprost promoted differentiation of mouse bone mesenchymal 
      stem cells (M-BMSCs) through the PI3K-AKT pathway. In co-culture, osteoblasts 
      stimulated with beraprost inhibited osteoclastogenesis in a rankl-dependent 
      manner. Bone mass of p53 knockout mice remained stable, regardless of the 
      administration of beraprost, indicating that p53 plays a vital role in the bone 
      mass regulation by beraprost. Mechanistic in vitro studies showed that p53 binds 
      to the promoter region of neuronal precursor cell-expressed developmentally 
      downregulated 4 (Nedd4) to promote its transcription. As a ubiquitinating enzyme, 
      Nedd4 binds to runt-related transcription factor 2 (Runx2), which results in its 
      ubiquitination and subsequent degradation. These data indicate that the 
      p53-Nedd4-Runx2 axis is an effective regulator of bone formation and highlight 
      the potential of beraprost as a therapeutic drug for postmenopausal osteoporosis.
FAU - Zheng, Huo-Liang
AU  - Zheng HL
AD  - Department of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong 
      University School of Medicine, 200082, Shanghai, China.
FAU - Xu, Wen-Ning
AU  - Xu WN
AD  - Department of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong 
      University School of Medicine, 200082, Shanghai, China.
FAU - Zhou, Wen-Sheng
AU  - Zhou WS
AD  - Department of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong 
      University School of Medicine, 200082, Shanghai, China.
FAU - Yang, Run-Ze
AU  - Yang RZ
AD  - Department of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong 
      University School of Medicine, 200082, Shanghai, China.
FAU - Chen, Peng-Bo
AU  - Chen PB
AD  - Department of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong 
      University School of Medicine, 200082, Shanghai, China.
FAU - Liu, Tao
AU  - Liu T
AUID- ORCID: 0000-0002-1482-4858
AD  - Department of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong 
      University School of Medicine, 200082, Shanghai, China.
FAU - Jiang, Lei-Sheng
AU  - Jiang LS
AD  - Department of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong 
      University School of Medicine, 200082, Shanghai, China. 
      jiangleisheng@xinhuamed.com.cn.
FAU - Jiang, Sheng-Dan
AU  - Jiang SD
AUID- ORCID: 0000-0001-6653-1881
AD  - Department of Clinic of Spine Center, Xinhua Hospital, Shanghai Jiaotong 
      University School of Medicine, 200082, Shanghai, China. 
      jiangshengdan@xinhuamed.com.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210515
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (N4BP1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (RUNX2 protein, human)
RN  - 35E3NJJ4O6 (beraprost)
RN  - DCR9Z582X0 (Epoprostenol)
SB  - IM
MH  - Core Binding Factor Alpha 1 Subunit/*metabolism
MH  - Epoprostenol/*analogs & derivatives/pharmacology/therapeutic use
MH  - Humans
MH  - Nuclear Proteins/*metabolism
MH  - Osteoporosis, Postmenopausal/*genetics
MH  - Platelet Aggregation Inhibitors/pharmacology/*therapeutic use
MH  - RNA-Binding Proteins/*metabolism
MH  - Ubiquitination
PMC - PMC8124066
COIS- The authors declare no competing interests.
EDAT- 2021/05/17 06:00
MHDA- 2021/10/15 06:00
PMCR- 2021/05/15
CRDT- 2021/05/16 20:56
PHST- 2021/01/15 00:00 [received]
PHST- 2021/04/30 00:00 [accepted]
PHST- 2021/04/28 00:00 [revised]
PHST- 2021/05/16 20:56 [entrez]
PHST- 2021/05/17 06:00 [pubmed]
PHST- 2021/10/15 06:00 [medline]
PHST- 2021/05/15 00:00 [pmc-release]
AID - 10.1038/s41419-021-03784-8 [pii]
AID - 3784 [pii]
AID - 10.1038/s41419-021-03784-8 [doi]
PST - epublish
SO  - Cell Death Dis. 2021 May 15;12(5):497. doi: 10.1038/s41419-021-03784-8.