PMID- 30154485
OWN - NLM
STAT- MEDLINE
DCOM- 20190517
LR  - 20210302
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 50
IP  - 8
DP  - 2018 Aug 28
TI  - PRMT1 mediates RANKL-induced osteoclastogenesis and contributes to bone loss in 
      ovariectomized mice.
PG  - 1-15
LID - 10.1038/s12276-018-0134-x [doi]
LID - 111
AB  - Protein arginine methylation is a novel form of posttranslational modification 
      mediated by protein arginine methyltransferase (PRMTs). PRMT1, a major isoform of 
      the PRMT family, is responsible for various biological functions, including 
      cellular differentiation. Although the important function that PRMT1 plays in 
      various tissues is being increasingly recognized, its role in receptor activation 
      of NF-kappaB ligand (RANKL)-induced osteoclastogenesis or osteoporosis has not yet 
      been described. Here, we show that PRMT1 is essential for RANKL-induced 
      osteoclastogenesis in vitro and for bone loss in vivo. RANKL treatment increased 
      the expression of PRMT1 and its nuclear localization in bone marrow-derived 
      macrophages (BMDMs) in a c-Jun N-terminal kinase (JNK)-dependent manner. 
      Silencing PRMT1 attenuated RANKL-induced osteoclastogenesis by decreasing 
      tartrate-resistant acid phosphatase (TRAP)-positive cells and inhibiting F-actin 
      ring formation and bone resorption, which was confirmed in a separate experiment 
      using haploinsufficient cells from PRMT1(+/-) mice. Our results also revealed 
      that PRMT1 regulates the transcription activity of NF-kappaB by directly interacting 
      with it in RANKL-treated BMDMs. An in vivo study showed that the 
      haploinsufficiency of PRMT1 reduced the enzyme activity of TRAP and increased the 
      bone mineral density in the metaphysis of ovariectomized (OVX) mice. Finally, 
      treatment with estrogen (E2) downregulated the RANKL-induced expression of PRMT1, 
      suggesting that estrogen may exert an inhibitory effect on osteoclastogenesis by 
      suppressing PRMT1 expression. Our results suggest that PRMT1 plays an important 
      role in the progression of osteoporosis and that it might be a good therapeutic 
      target for postmenopausal osteoporosis.
FAU - Choi, Joo-Hee
AU  - Choi JH
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, 61186, Republic of Korea.
FAU - Jang, Ah-Ra
AU  - Jang AR
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, 61186, Republic of Korea.
FAU - Kim, Dong-Il
AU  - Kim DI
AD  - Department of Physiology, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, 61186, Republic of Korea.
FAU - Park, Min-Jung
AU  - Park MJ
AD  - Department of Molecular and Integrative Physiology, University of Michigan 
      Medical School, Ann Arbor, MI, 48109, USA.
FAU - Lim, Seul-Ki
AU  - Lim SK
AD  - Microbiology and Functionality Research Group, World Institute of Kimchi, 
      Gwangju, 61755, Republic of Korea.
FAU - Kim, Myung-Sun
AU  - Kim MS
AD  - Department of Orthopaedic Surgery, Chonnam National University Medical School, 
      Gwangju, 61469, Republic of Korea.
FAU - Park, Jong-Hwan
AU  - Park JH
AD  - Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National 
      University, Gwangju, 61186, Republic of Korea. jonpark@jnu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180828
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Estrogens)
RN  - 0 (RANK Ligand)
RN  - 0 (Transcription Factor RelA)
RN  - EC 2.1.1.319 (Prmt1 protein, mouse)
RN  - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Bone Resorption/*enzymology/*pathology
MH  - Cell Differentiation/drug effects
MH  - Down-Regulation/drug effects
MH  - Estrogens/pharmacology
MH  - Female
MH  - Haploinsufficiency
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Macrophages/drug effects/metabolism
MH  - Mice, Inbred C57BL
MH  - Osteoclasts/drug effects/metabolism/pathology
MH  - Osteogenesis/*drug effects
MH  - *Ovariectomy
MH  - Phenotype
MH  - Protein Binding/drug effects
MH  - Protein-Arginine N-Methyltransferases/*metabolism
MH  - RANK Ligand/*pharmacology
MH  - Transcription Factor RelA/metabolism
MH  - Up-Regulation/drug effects
PMC - PMC6113271
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/08/30 06:00
MHDA- 2019/05/18 06:00
PMCR- 2018/08/28
CRDT- 2018/08/30 06:00
PHST- 2018/01/03 00:00 [received]
PHST- 2018/05/29 00:00 [accepted]
PHST- 2018/05/14 00:00 [revised]
PHST- 2018/08/30 06:00 [entrez]
PHST- 2018/08/30 06:00 [pubmed]
PHST- 2019/05/18 06:00 [medline]
PHST- 2018/08/28 00:00 [pmc-release]
AID - 10.1038/s12276-018-0134-x [pii]
AID - 134 [pii]
AID - 10.1038/s12276-018-0134-x [doi]
PST - epublish
SO  - Exp Mol Med. 2018 Aug 28;50(8):1-15. doi: 10.1038/s12276-018-0134-x.