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conferenceseries
.com
Volume 5, Issue 2 (Suppl)
Transcriptomics, an open access journal
ISSN: 2329-8936
Molecular Biology 2017
August 31-September 01, 2017
2
nd
International Conference on
August 31-September 01, 2017 Philadelphia, USA
Molecular Biology, Nucleic Acids &
Molecular Medicine
miR-375-3p negatively regulates osteogenesis by targeting LRP5 and β-catenin
Tianhao Sun, Chen-Tian Li, Frankie Leung
and
William W Lu
The University of Hong Kong, China
W
nt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were
regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we
investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated
osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition,
the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis. Secondly, miR-375-3p
targeted low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of the Wnt signaling pathways and β-catenin
as determined by luciferase activity assay and it decreased the expression levels of LRP5 and β-catenin. Thirdly, the decline
of protein levels of β-catenin was determined by immunocytochemistry and immunofluorescence. Finally, silence of LRP5 in
osteoblast precursor cells resulted in diminished cell viability and cell proliferation as detected by WST-1-based colorimetric
assay. Additionally, all the parameters including the relative bone volume from µCT measurement suggested that LRP5
knockout in mice resulted in a looser and worse-connected trabecula. The mRNA levels of important negative modulators
relating to osteogenesis increased after the functions of LRP5 were blocked in mice. Finally, the expression levels of LRP5
increased during the osteogenesis of MC3T3-E1, while the levels of β-catenin decreased in bone tissues from osteoporotic
patients with vertebral compression fractures. In conclusion, we revealed miR-375-3p negatively regulated osteogenesis by
targeting LRP5 and β-catenin. In addition, loss of functions of LRP5 damaged bone formation
in vivo.
Clinically, miR-375-
3p and its targets might be used as diagnostic biomarkers for osteoporosis and might be also as novel therapeutic agents in
osteoporosis treatment. The relevant products of miR-375-3p might be developed into molecular drugs in the future. These
molecules could be used in translational medicine.
sunmishu@126.comTranscriptomics 2017, 5:2 (Suppl)
DOI: 10.4172/2329-8936-C1-013