PMID- 31985020
OWN - NLM
STAT- MEDLINE
DCOM- 20201123
LR  - 20211204
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 45
IP  - 4
DP  - 2020 Apr
TI  - Adiponectin inhibits the differentiation and maturation of osteoclasts via the 
      mTOR pathway in multiple myeloma.
PG  - 1112-1120
LID - 10.3892/ijmm.2020.4475 [doi]
AB  - The present study sought to investigate the correlation between adipose cytokines 
      (visfatin, leptin and adiponectin) and markers of multiple myeloma bone disease, 
      and to determine the effects and mechanism of action of adiponectin on the 
      differentiation and maturation of osteoclasts in multiple myeloma (MM). The 
      levels of visfatin, leptin and adiponectin were measured. Their association with 
      the indices of myeloma tumor load and bone disease were analyzed. Reverse 
      transcription‑quantitative PCR was used to detect the expression of receptor 
      activator of nuclear factor‑kappaB ligand (RANKL), osteoclast associated Ig‑like 
      receptor (OSCAR), tartrate‑resistant acid phosphatase (TRAP) and Cathepsin K 
      genes. Flow cytometry was used to detect the expression of adiponectin receptor 1 
      (AdipoR1) and the phosphorylation of the mechanistic target of rapamycin kinase 
      (mTOR) pathway‑associated proteins mTOR and eukaryotic translation initiation 
      factor 4E‑binding protein (4EBP1). There were no significant correlations among 
      leptin, visfatin and the indexes of myeloma tumor load and bone disease. Serum 
      adiponectin levels were significantly lower in patients with newly diagnosed 
      multiple myeloma compared with healthy volunteers (12.37+/-3.13 vs. 13.80+/-0.95; 
      P<0.05). The number of mature osteoclasts in the adiponectin group was lower 
      compared with in the control group. Adiponectin also inhibited the mRNA 
      expression of the osteoclast‑associated factors RANKL, OSCAR, TRAP and Cathepsin 
      K. Comparison between the non‑adiponectin group and the adiponectin group 
      revealed that adiponectin increased the expression of AdipoR1 on the surface of 
      osteoclast precursor cells (26.21+/-4.27% vs. 29.86+/-6.23%; P<0.05) and reduced the 
      expression of phosphorylated (p‑)mTOR (7.89+/-1.00% vs. 5.91+/-1.26%; P<0.05) and 
      p‑4EBP1 (26.78+/-5.00% vs. 22.49+/-4.24%; P<0.05). The p‑mTOR and p‑4EBP1 levels in 
      the adiponectin + MHY1485 (an mTOR signaling pathway‑specific agonist) group were 
      significantly higher compared with those in the adiponectin group. It was 
      revealed that adiponectin may inhibit osteoclast differentiation and maturation 
      via the mTOR pathway. In conclusion, adiponectin inhibits the differentiation and 
      maturation of osteoclasts by increasing the expression of AdipoR1 and reducing 
      the phosphorylation levels of mTOR and 4EBP1 in patients with MM.
FAU - Liu, Zhaoyun
AU  - Liu Z
AD  - Department of Hematology, Tianjin Medical University General Hospital, Tianjin 
      300052, P.R. China.
FAU - Liu, Hui
AU  - Liu H
AD  - Department of Hematology, Tianjin Medical University General Hospital, Tianjin 
      300052, P.R. China.
FAU - Li, Yanqi
AU  - Li Y
AD  - Department of Hematology, Tianjin Medical University General Hospital, Tianjin 
      300052, P.R. China.
FAU - Wang, Yangyang
AU  - Wang Y
AD  - Department of Hematology, Tianjin Medical University General Hospital, Tianjin 
      300052, P.R. China.
FAU - Xing, Rui
AU  - Xing R
AD  - Department of Hematology, Tianjin Medical University General Hospital, Tianjin 
      300052, P.R. China.
FAU - Mi, Fu
AU  - Mi F
AD  - Department of Hematology, Tianjin Medical University General Hospital, Tianjin 
      300052, P.R. China.
FAU - Xiang, Chenhuan
AU  - Xiang C
AD  - Department of Hematology, Tianjin Medical University General Hospital, Tianjin 
      300052, P.R. China.
FAU - Fu, Rong
AU  - Fu R
AD  - Department of Hematology, Tianjin Medical University General Hospital, Tianjin 
      300052, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200124
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Adiponectin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adiponectin/*therapeutic use
MH  - Aged
MH  - Cell Differentiation/*drug effects
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoassay
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/metabolism
MH  - Osteoclasts/*cytology/*drug effects
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC7053860
EDAT- 2020/01/28 06:00
MHDA- 2020/11/24 06:00
PMCR- 2020/01/24
CRDT- 2020/01/28 06:00
PHST- 2019/06/02 00:00 [received]
PHST- 2019/12/10 00:00 [accepted]
PHST- 2020/01/28 06:00 [pubmed]
PHST- 2020/11/24 06:00 [medline]
PHST- 2020/01/28 06:00 [entrez]
PHST- 2020/01/24 00:00 [pmc-release]
AID - ijmm-45-04-1112 [pii]
AID - 10.3892/ijmm.2020.4475 [doi]
PST - ppublish
SO  - Int J Mol Med. 2020 Apr;45(4):1112-1120. doi: 10.3892/ijmm.2020.4475. Epub 2020 
      Jan 24.