PMID- 35846320
OWN - NLM
STAT- MEDLINE
DCOM- 20220719
LR  - 20220802
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 13
DP  - 2022
TI  - CD137 Regulates Bone Loss via the p53 Wnt/beta-Catenin Signaling Pathways in Aged 
      Mice.
PG  - 922501
LID - 10.3389/fendo.2022.922501 [doi]
LID - 922501
AB  - Senile osteoporosis is a chronic skeletal disease, leading to increased bone 
      brittleness and risk of fragile fractures. With the acceleration of population 
      aging, osteoporosis has gradually become one of the most serious and prevalent 
      problems worldwide. Bone formation is highly dependent on the proper osteogenic 
      differentiation of bone marrow mesenchymal stem cells (BMSCs) in the bone marrow 
      microenvironment, which is generated by the functional relationship among 
      different cell types, including osteoblasts, adipogenic cells, and bone marrow 
      stromal cells in the bone marrow. It is still not clear how osteoporosis is 
      caused by its molecular mechanism. With aging, bone marrow is able to restrain 
      osteogenesis. Discovering the underlying signals that oppose BMSC osteogenic 
      differentiation from the bone marrow microenvironment and identifying the unusual 
      changes in BMSCs with aging is important to elucidate possible mechanisms of 
      senile osteoporosis. We used 3 gene expression profiles (GSE35956, GSE35957, and 
      GSE35959) associated with osteoporosis. And a protein-protein interaction (PPI) 
      network was also built to identify the promising gene CD137. After that, we 
      performed in vivo experiments to verify its function and mechanism. In this 
      experiment, we found that significant bone loss was observed in aged 
      (18-month-old) mice compared with young (6-month-old) mice. The adipose tissue in 
      bone marrow cavity from aged mice reached above 10 times more than young mice. 
      Combining bioinformatics analysis and vivo experiments, we inferred that CD137 
      might be involved in the p53 and canonical Wnt/beta-catenin signaling pathways and 
      thereby influenced bone mass through regulation of marrow adipogenesis. 
      Importantly, osteoporosis can be rescued by blocking CD137 signaling in vivo. Our 
      research will contribute to our understanding not only of the pathogenesis of 
      age-related bone loss but also to the identification of new targets for treating 
      senile osteoporosis.
CI  - Copyright (c) 2022 Han, Wang, Zhou, Zhang and Wan.
FAU - Han, Jiyu
AU  - Han J
AD  - Department of Orthopedics, Tongji Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
AD  - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry 
      of Education, Shanghai, China.
FAU - Wang, Yanhong
AU  - Wang Y
AD  - Department of Orthopedics, Tongji Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
AD  - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry 
      of Education, Shanghai, China.
FAU - Zhou, Haichao
AU  - Zhou H
AD  - Department of Orthopedics, Tongji Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
AD  - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry 
      of Education, Shanghai, China.
FAU - Zhang, Yingqi
AU  - Zhang Y
AD  - Department of Orthopedics, Tongji Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
FAU - Wan, Daqian
AU  - Wan D
AD  - Department of Orthopedics, Tongji Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
AD  - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry 
      of Education, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220630
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (4-1BB Ligand)
RN  - 0 (Tnfsf9 protein, mouse)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - 4-1BB Ligand/*metabolism
MH  - Animals
MH  - *Mesenchymal Stem Cells
MH  - Mice
MH  - Osteogenesis
MH  - *Osteoporosis/genetics/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Wnt Signaling Pathway
PMC - PMC9279613
OTO - NOTNLM
OT  - Bioinformatics
OT  - CD 137
OT  - gene expression
OT  - hub genes
OT  - osteoporosis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/19 06:00
MHDA- 2022/07/20 06:00
PMCR- 2022/01/01
CRDT- 2022/07/18 04:00
PHST- 2022/04/18 00:00 [received]
PHST- 2022/06/06 00:00 [accepted]
PHST- 2022/07/18 04:00 [entrez]
PHST- 2022/07/19 06:00 [pubmed]
PHST- 2022/07/20 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2022.922501 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2022 Jun 30;13:922501. doi: 
      10.3389/fendo.2022.922501. eCollection 2022.