PMID- 36060812
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221022
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 10
DP  - 2022
TI  - The crosstalk between MYC and mTORC1 during osteoclastogenesis.
PG  - 920683
LID - 10.3389/fcell.2022.920683 [doi]
LID - 920683
AB  - Osteoclasts are bone-resorbing cells that undergo extensive changes in morphology 
      throughout their differentiation. Altered osteoclast differentiation and activity 
      lead to changes in pathological bone resorption. The mammalian target of 
      rapamycin (mTOR) is a kinase, and aberrant mTOR complex 1 (mTORC1) signaling is 
      associated with altered bone homeostasis. The activation of mTORC1 is 
      biphasically regulated during osteoclastogenesis; however, the mechanism behind 
      mTORC1-mediated regulation of osteoclastogenesis and bone resorption is 
      incompletely understood. Here, we found that MYC coordinates the dynamic 
      regulation of mTORC1 activation during osteoclastogenesis. MYC-deficiency blocked 
      the early activation of mTORC1 and also reversed the decreased activity of mTORC1 
      at the late stage of osteoclastogenesis. The suppression of mTORC1 activity by 
      rapamycin in mature osteoclasts enhances bone resorption activity despite the 
      indispensable role of high mTORC1 activation in osteoclast formation in both 
      mouse and human cells. Mechanistically, MYC induces Growth arrest and DNA 
      damage-inducible protein (GADD34) expression and suppresses mTORC1 activity at 
      the late phase of osteoclastogenesis. Taken together, our findings identify a 
      MYC-GADD34 axis as an upstream regulator of dynamic mTORC1 activation in 
      osteoclastogenesis and highlight the interplay between MYC and mTORC1 pathways in 
      determining osteoclast activity.
CI  - Copyright (c) 2022 Bae, Oh, Tsai, Park, Greenblatt, Giannopoulou and Park-Min.
FAU - Bae, Seyeon
AU  - Bae S
AD  - Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research 
      Center, Hospital for Special Surgery, New York, NY, United States.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, United 
      States.
FAU - Oh, Brian
AU  - Oh B
AD  - Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research 
      Center, Hospital for Special Surgery, New York, NY, United States.
FAU - Tsai, Jefferson
AU  - Tsai J
AD  - Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research 
      Center, Hospital for Special Surgery, New York, NY, United States.
FAU - Park, Peter Sang Uk
AU  - Park PSU
AD  - Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research 
      Center, Hospital for Special Surgery, New York, NY, United States.
FAU - Greenblatt, Matthew Blake
AU  - Greenblatt MB
AD  - Department of Pathology, Weill Cornell Medical College, New York, NY, United 
      States.
FAU - Giannopoulou, Eugenia G
AU  - Giannopoulou EG
AD  - Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research 
      Center, Hospital for Special Surgery, New York, NY, United States.
AD  - Biological Sciences Department, New York City College of Technology, City 
      University of New York, Brooklyn, NY, United States.
FAU - Park-Min, Kyung-Hyun
AU  - Park-Min KH
AD  - Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research 
      Center, Hospital for Special Surgery, New York, NY, United States.
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY, United 
      States.
AD  - BCMB Allied Program, Weill Cornell Graduate School of Medical Sciences, New York, 
      NY, United States.
LA  - eng
GR  - R01 AR069562/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20220819
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC9437285
OTO - NOTNLM
OT  - GADD34 (PPP1R15A)
OT  - MYC (c-myc)
OT  - bone resorption
OT  - mTORC1 (mechanistic target of rapamycin complex 1)
OT  - osteoclast (OC)
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- 2022/09/06 06:00
MHDA- 2022/09/06 06:01
PMCR- 2022/01/01
CRDT- 2022/09/05 03:59
PHST- 2022/04/14 00:00 [received]
PHST- 2022/07/19 00:00 [accepted]
PHST- 2022/09/05 03:59 [entrez]
PHST- 2022/09/06 06:00 [pubmed]
PHST- 2022/09/06 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 920683 [pii]
AID - 10.3389/fcell.2022.920683 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2022 Aug 19;10:920683. doi: 10.3389/fcell.2022.920683. 
      eCollection 2022.