PMID- 35742976
OWN - NLM
STAT- MEDLINE
DCOM- 20220627
LR  - 20240214
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 12
DP  - 2022 Jun 10
TI  - Effect of Anti-Osteoporotic Treatments on Circulating and Bone MicroRNA Patterns 
      in Osteopenic ZDF Rats.
LID - 10.3390/ijms23126534 [doi]
LID - 6534
AB  - Bone fragility is an adverse outcome of type 2 diabetes mellitus (T2DM). The 
      underlying molecular mechanisms have, however, remained largely unknown. 
      MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression in 
      health and disease states. The aim of this study was to investigate the 
      genome-wide regulation of miRNAs in T2DM bone disease by analyzing serum and bone 
      tissue samples from a well-established rat model of T2DM, the Zucker Diabetic 
      Fatty (ZDF) model. We performed small RNA-sequencing analysis to detect 
      dysregulated miRNAs in the serum and ulna bone of the ZDF model under placebo and 
      also under anti-sclerostin, PTH, and insulin treatments. The dysregulated 
      circulating miRNAs were investigated for their cell-type enrichment to identify 
      putative donor cells and were used to construct gene target networks. Our results 
      show that unique sets of miRNAs are dysregulated in the serum (n = 12, FDR < 0.2) 
      and bone tissue (n = 34, FDR < 0.2) of ZDF rats. Insulin treatment was found to 
      induce a strong dysregulation of circulating miRNAs which are mainly involved in 
      metabolism, thereby restoring seven circulating miRNAs in the ZDF model to normal 
      levels. The effects of anti-sclerostin treatment on serum miRNA levels were 
      weaker, but affected miRNAs were shown to be enriched in bone tissue. PTH 
      treatment did not produce any effect on circulating or bone miRNAs in the ZDF 
      rats. Altogether, this study provides the first comprehensive insights into the 
      dysregulation of bone and serum miRNAs in the context of T2DM and the effect of 
      insulin, PTH, and anti-sclerostin treatments on circulating miRNAs.
FAU - Carro Vazquez, David
AU  - Carro Vazquez D
AUID- ORCID: 0000-0001-7957-3319
AD  - TAmiRNA GmbH, Department of Research, Leberstrasse 20, 1110 Vienna, Austria.
FAU - Emini, Lejla
AU  - Emini L
AD  - Center for Healthy Aging and Department of Medicine III, Technische Universitat 
      Dresden, 01069 Dresden, Germany.
FAU - Rauner, Martina
AU  - Rauner M
AD  - Center for Healthy Aging and Department of Medicine III, Technische Universitat 
      Dresden, 01069 Dresden, Germany.
FAU - Hofbauer, Christine
AU  - Hofbauer C
AD  - Center for Healthy Aging and Department of Medicine III, Technische Universitat 
      Dresden, 01069 Dresden, Germany.
FAU - Grillari, Johannes
AU  - Grillari J
AUID- ORCID: 0000-0001-5474-6332
AD  - Ludwig Boltzmann Institute for Traumatology in Cooperation with AUVA, Ludwig 
      Boltzmann Society, 1200 Vienna, Austria.
AD  - Institute of Molecular Biotechnology, University of Natural Resources and Life 
      Sciences, 1180 Vienna, Austria.
AD  - Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria.
FAU - Diendorfer, Andreas B
AU  - Diendorfer AB
AUID- ORCID: 0000-0003-0331-9685
AD  - TAmiRNA GmbH, Department of Research, Leberstrasse 20, 1110 Vienna, Austria.
FAU - Eastell, Richard
AU  - Eastell R
AD  - Academic Unit of Bone Metabolism and Mellanby Centre for Bone Research, 
      University of Sheffield, Sheffield S10 2RX, UK.
FAU - Hofbauer, Lorenz C
AU  - Hofbauer LC
AD  - Center for Healthy Aging and Department of Medicine III, Technische Universitat 
      Dresden, 01069 Dresden, Germany.
FAU - Hackl, Matthias
AU  - Hackl M
AD  - TAmiRNA GmbH, Department of Research, Leberstrasse 20, 1110 Vienna, Austria.
AD  - Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria.
LA  - eng
GR  - MR/P020941/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20220610
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Insulin)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Animals
MH  - Bone and Bones/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Insulin
MH  - *MicroRNAs
MH  - Rats
MH  - Rats, Zucker
PMC - PMC9224326
OTO - NOTNLM
OT  - ZDF
OT  - biomarker
OT  - circulating microRNA
OT  - microRNA
OT  - next-generation sequencing
OT  - osteoporosis
OT  - type 2 diabetes
COIS- D.C.V. and A.B.D. are employed at TAmiRNA GmbH. M.H. is the CEO and cofounder of 
      TAmiRNA GmbH.
EDAT- 2022/06/25 06:00
MHDA- 2022/06/28 06:00
PMCR- 2022/06/10
CRDT- 2022/06/24 01:21
PHST- 2022/05/06 00:00 [received]
PHST- 2022/06/03 00:00 [revised]
PHST- 2022/06/08 00:00 [accepted]
PHST- 2022/06/24 01:21 [entrez]
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/06/28 06:00 [medline]
PHST- 2022/06/10 00:00 [pmc-release]
AID - ijms23126534 [pii]
AID - ijms-23-06534 [pii]
AID - 10.3390/ijms23126534 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Jun 10;23(12):6534. doi: 10.3390/ijms23126534.