PMID- 37735431
OWN - NLM
STAT- MEDLINE
DCOM- 20230927
LR  - 20231120
IS  - 1749-799X (Electronic)
IS  - 1749-799X (Linking)
VI  - 18
IP  - 1
DP  - 2023 Sep 21
TI  - DAP1 regulates osteoblast autophagy via the ATG16L1-LC3 axis in Graves' 
      disease-induced osteoporosis.
PG  - 711
LID - 10.1186/s13018-023-04171-z [doi]
LID - 711
AB  - OBJECTIVE: This study aimed to uncover a critical protein and its mechanisms in 
      modulating autophagy in Graves' disease (GD)-induced osteoporosis (OP). METHODS: 
      We discovered the target protein, death-associated protein 1 (DAP1), using bone 
      proteomics analysis. Furthermore, genetic overexpression and knockdown (KD) of 
      DAP1 in bone and MC3T3-E1 cells revealed DAP1 effects on autophagy and osteogenic 
      markers, and autophagic vacuoles in cells were detected using transmission 
      electron microscopy and the microtubule-associated protein 1 light chain 3 alpha 
      (MAP1LC3/LC3) dual fluorescence system. An autophagy polymerase chain reaction 
      (PCR) array kit was used to identify the key molecules associated with 
      DAP1-regulated autophagy. RESULTS: DAP1 levels were significantly higher in the 
      bone tissue of GD mice and MC3T3-E1 cells treated with triiodothyronine (T3). 
      DAP1 overexpression reduced LC3 lipidation, autophagic vacuoles, RUNX family 
      transcription factor 2 (RUNX2), and osteocalcin (OCN) expression in MC3T3-E1 
      cells, whereas DAP1 KD reversed these changes. In vivo experiments revealed that 
      GD mice with DAP1 KD had greater bone mass than control mice. DAP1-overexpressing 
      (OE) cells had lower levels of phosphorylated autophagy-related 16-like 1 
      (ATG16L1) and LC3 lipidation, whereas DAP1-KD cells had higher levels. 
      CONCLUSIONS: DAP1 was found to be a critical regulator of autophagy homeostasis 
      in GD mouse bone tissue and T3-treated osteoblasts because it negatively 
      regulated autophagy and osteogenesis in osteoblasts via the ATG16L1-LC3 axis.
CI  - (c) 2023. BioMed Central Ltd., part of Springer Nature.
FAU - Gao, Mingdong
AU  - Gao M
AD  - The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, 
      China.
AD  - Department Pediatrics, Gansu Provincial Hospital, Lanzhou, 730030, Gansu, China.
AD  - Clinical Research Center for Metabolic Diseases, Lanzhou, 730030, Gansu, China.
FAU - Du, Zouxi
AU  - Du Z
AD  - The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, 
      China.
FAU - Dong, Qianqian
AU  - Dong Q
AD  - The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, 
      China.
FAU - Su, Shan
AU  - Su S
AD  - The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, 
      China.
FAU - Tian, Limin
AU  - Tian L
AD  - The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, 
      China. tlm6666@sina.com.
AD  - Clinical Research Center for Metabolic Diseases, Lanzhou, 730030, Gansu, China. 
      tlm6666@sina.com.
AD  - Department of Endocrinology, Gansu Provincial Hospital, No. 204 West Donggang 
      Road, Lanzhou, 730030, Gansu, China. tlm6666@sina.com.
LA  - eng
GR  - 82060152/National Social Science Fund of China/
GR  - 21JR11RA192/Natural Science Foundation of Gansu Province/
GR  - 2018-RC-79/Lanzhou City Talent Innovation and Entrepreneurship Project/
PT  - Journal Article
DEP - 20230921
PL  - England
TA  - J Orthop Surg Res
JT  - Journal of orthopaedic surgery and research
JID - 101265112
RN  - 0 (Atg16l1 protein, mouse)
RN  - 0 (Map1lc3b protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Autophagy/genetics
MH  - Bone and Bones
MH  - *Graves Disease
MH  - Osteoblasts
MH  - *Osteoporosis/etiology
PMC - PMC10512661
OTO - NOTNLM
OT  - Autophagy
OT  - Death-associated protein 1
OT  - Graves' disease
OT  - Osteoblasts
OT  - Osteoporosis
COIS- The authors declare that they have no competing interests.
EDAT- 2023/09/22 06:42
MHDA- 2023/09/25 06:42
PMCR- 2023/09/21
CRDT- 2023/09/22 00:46
PHST- 2023/07/04 00:00 [received]
PHST- 2023/09/07 00:00 [accepted]
PHST- 2023/09/25 06:42 [medline]
PHST- 2023/09/22 06:42 [pubmed]
PHST- 2023/09/22 00:46 [entrez]
PHST- 2023/09/21 00:00 [pmc-release]
AID - 10.1186/s13018-023-04171-z [pii]
AID - 4171 [pii]
AID - 10.1186/s13018-023-04171-z [doi]
PST - epublish
SO  - J Orthop Surg Res. 2023 Sep 21;18(1):711. doi: 10.1186/s13018-023-04171-z.