PMID- 29353038
OWN - NLM
STAT- MEDLINE
DCOM- 20180222
LR  - 20201209
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 496
IP  - 3
DP  - 2018 Feb 12
TI  - Cereblon (CRBN) deletion reverses streptozotocin induced diabetic osteoporosis in 
      mice.
PG  - 967-974
LID - S0006-291X(18)30110-4 [pii]
LID - 10.1016/j.bbrc.2018.01.095 [doi]
AB  - Diabetes mellitus is a major cause to induce osteoporosis. Though the 
      pathogenesis of osteoporosis progression has been well investigated, its still 
      not fully understood. Recently, cereblon (CRBN) was considered as a negative 
      modulator of adenosine monophosphate-activated protein kinase (AMPK) in vitro and 
      in vivo. Here, we presented results indicating that CRBN could effectively 
      regulate osteoporosis development. In STZ-induced wild type (WT) mice with 
      diabetes, the osteoclasts were highly increased along with the deterioration of 
      bone structure. However, CRBN knockout (KO) reduced blood glucose the levels and 
      attenuated insulin resistance. What's more, CRBN ablation suppressed osteoclast 
      differentiation and rescued diabetic bone loss in vivo, accompanied with 
      decreased receptor activator of NF-kB ligand (RANKL), RANKL/osteoprotegerin 
      (OPG), and tartrate-resistant acid phosphatase (TRAP) levels, as well as improved 
      AMP-activated kinase (AMPK) alpha/acetyl-CoA carboxylase (ACC)alphaactivation. In vitro, 
      suppressing CRBN expression could reduce RANKL-induced osteoclastogenesis, 
      supported by the reduction of TRAP-positive cells. CRBN knockdown (KD) obviously 
      reduced RANKL-induced activity of IkappaBalpha/nuclear factor-kappaB (NF-kappaB) pathway. In 
      addition, osteoclast-specific genes expression levels stimulated by RANKL were 
      also decreased by CRBN silence. More importantly, CRBN blockage increased 
      phosphorylated AMPK-alpha and ACC-alpha expressions in RANKL-incubated cells. However, 
      these processes could be abolished by suppressing AMPK-alpha with its inhibitor, 
      Compound C. Collectively, our data suggested that CRBN is a potential treatment 
      option against diabetes-induced osteolytic bone disease.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Yao, Cong
AU  - Yao C
AD  - Department of Plastic Surgery, The Second Affiliated Hospital of Xi'an Jiao Tong 
      University, Xi'an, 710004, China.
FAU - Guo, Xiong
AU  - Guo X
AD  - Public Health School of Xi'an Jiao Tong University, Xi'an, 710061, China. 
      Electronic address: guox@mail.xjtu.edu.cn.
FAU - Yao, Wan-Xia
AU  - Yao WX
AD  - Department of Radiotherapy, The First Affiliated Hospital of Xi'an Jiao Tong 
      University, Xi'an, 710061, China.
FAU - Zhang, Chun
AU  - Zhang C
AD  - Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiao Tong 
      University, Xi'an, 710004, China.
LA  - eng
PT  - Journal Article
DEP - 20180117
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Crbn protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (Immunologic Factors)
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Cytokines/*immunology
MH  - Diabetes Mellitus, Experimental/complications/*immunology/*pathology
MH  - Immunologic Factors/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/genetics/*immunology
MH  - Osteoporosis/etiology/*immunology/*pathology
OTO - NOTNLM
OT  - AMPK-alpha/ACC-alpha
OT  - CRBN
OT  - Diabetic osteoporosis
OT  - IkappaBalpha/NF-kappaB
OT  - Osteoclast
EDAT- 2018/01/22 06:00
MHDA- 2018/02/23 06:00
CRDT- 2018/01/22 06:00
PHST- 2018/01/09 00:00 [received]
PHST- 2018/01/14 00:00 [accepted]
PHST- 2018/01/22 06:00 [pubmed]
PHST- 2018/02/23 06:00 [medline]
PHST- 2018/01/22 06:00 [entrez]
AID - S0006-291X(18)30110-4 [pii]
AID - 10.1016/j.bbrc.2018.01.095 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Feb 12;496(3):967-974. doi: 
      10.1016/j.bbrc.2018.01.095. Epub 2018 Jan 17.