PMID- 38105757
OWN - NLM
STAT- MEDLINE
DCOM- 20240131
LR  - 20240131
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 326
IP  - 2
DP  - 2024 Feb 1
TI  - DNA methylation of promoter region inhibits galectin-1 expression in BMSCs of 
      aged mice.
PG  - C429-C441
LID - 10.1152/ajpcell.00334.2023 [doi]
AB  - Senile osteoporosis increases fracture risks. Bone marrow stromal cells (BMSCs) 
      are sensitive to aging. Deep insights into BMSCs aging are vital to elucidate the 
      mechanisms underlying age-related bone loss. Recent advances showed that 
      osteoporosis is associated with aberrant DNA methylation of many susceptible 
      genes. Galectin-1 (Gal-1) has been proposed as a mediator of BMSCs functions. In 
      our previous study, we showed that Gal-1 was downregulated in aged BMSCs and 
      global deletion of Gal-1 in mice caused bone loss via impaired osteogenesis 
      potential of BMSCs. Gal-1 promoter is featured by CpG islands. However, there are 
      no reports concerning the DNA methylation status in Gal-1 promoter during 
      osteoporosis. In the current study, we sought to investigate the role of DNA 
      methylation in Gal-1 downregulation in aged BMSCs. The potential for anti-bone 
      loss therapy based on modulating DNA methylation is explored. Our results showed 
      that Dnmt3b-mediated Gal-1 promoter DNA hypermethylation plays an important role 
      in Gal-1 downregulation in aged BMSCs, which inhibited beta-catenin binding on Gal-1 
      promoter. Bone loss of aged mice was alleviated in response to in vivo deletion 
      of Dnmt3b from BMSCs. Finally, when bone marrow of young wild-type (WT) mice or 
      young Dnmt3b(Prx1-Cre) mice was transplanted into aged WT mice, Gal-1 level in 
      serum and trabecular bone mass were elevated in recipient aged WT mice. Our study 
      will benefit for deeper insights into the regulation mechanisms of Gal-1 
      expression in BMSCs during osteoporosis development, and for the discovery of new 
      therapeutic targets for osteoporosis via modulating DNA methylation status.NEW & 
      NOTEWORTHY There is Dnmt3b-mediated DNA methylation in Gal-1 promoter in aged 
      bone marrow stromal cell (BMSC). DNA methylation causes Gal-1 downregulation and 
      osteogenesis attenuation of aged BMSC. DNA methylation blocks beta-catenin binding 
      on Gal-1 promoter. Bone loss of aged mice is alleviated by in vivo deletion of 
      Dnmt3b from BMSC.
FAU - Tang, Liang
AU  - Tang L
AD  - Department of Orthopedic Surgery, Tongren Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai, People's Republic of China.
FAU - Zhang, Yang-Yang
AU  - Zhang YY
AD  - Department of Orthopedic Surgery, Tongren Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai, People's Republic of China.
FAU - Liu, Wen-Jun
AU  - Liu WJ
AD  - Department of Orthopedic Surgery, Tongren Hospital, Shanghai Jiao Tong University 
      School of Medicine, Shanghai, People's Republic of China.
FAU - Fu, Qiang
AU  - Fu Q
AD  - Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, People's Republic of China.
FAU - Zhao, Jian
AU  - Zhao J
AD  - Department of Orthopedics, Second Affiliated Hospital of Naval Medical 
      University, Shanghai, People's Republic of China.
FAU - Liu, Yan-Bin
AU  - Liu YB
AUID- ORCID: 0009-0002-3573-7478
AD  - Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, People's Republic of China.
LA  - eng
GR  - 20214Y008/Foundation of shanghai health and family planning commission/
GR  - TRYJ(LC)04/Research fund of shanghai Tongren hospital of shanghai jiaotong 
      university school of medicine/
PT  - Journal Article
DEP - 20231218
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (beta Catenin)
RN  - 0 (Galectin 1)
RN  - 59921-69-6 (1-nitrohydroxyphenyl-N-benzoylalanine)
RN  - 0 (Benzamides)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Animals
MH  - Mice
MH  - DNA Methylation/genetics
MH  - beta Catenin/metabolism
MH  - Galectin 1/genetics/metabolism
MH  - Osteogenesis/genetics
MH  - *Osteoporosis/genetics/metabolism
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Cell Differentiation
MH  - Bone Marrow Cells/metabolism
MH  - *Benzamides
MH  - Tyrosine/*analogs & derivatives
OTO - NOTNLM
OT  - DNA methylation
OT  - bone marrow stromal cells
OT  - galectin-1
OT  - osteoporosis
OT  - beta-catenin
EDAT- 2023/12/18 06:42
MHDA- 2024/01/31 06:42
CRDT- 2023/12/18 04:22
PHST- 2024/01/31 06:42 [medline]
PHST- 2023/12/18 06:42 [pubmed]
PHST- 2023/12/18 04:22 [entrez]
AID - 10.1152/ajpcell.00334.2023 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2024 Feb 1;326(2):C429-C441. doi: 
      10.1152/ajpcell.00334.2023. Epub 2023 Dec 18.