MicroRNA-451 blockade promotes osteoblastic differentiation and skeletal anabolic effects by promoting YWHAZ-mediated RUNX2 protein stabilization

MedChemComm
Jieen PanZhongwei Zhang

Abstract

Background: senile osteoporosis researchers are now seeking to promote osteoblastogenesis and resultant bone formation to directly counteract age-related bone loss. Targeting microRNA (miRNA) activity in adult osteoblasts may be a successful therapeutic strategy for age-related bone loss. We investigated the mechanism(s) by which miRNAs negatively regulate osteoblastogenesis and bone formation in vitro and in vivo. Methods: we performed a miRNA microarray screen followed by PCR validation in adult bone marrow-derived mesenchymal stem cells during the proliferation-to-mineralization transition to identify downregulated miRNAs, most notably miR-451. Primary human calvarial pre-osteoblasts were isolated and transfected with miR-451's agomir or antagomir for in vitro assays. Bioinformatics analysis and in vitro experiments verified YWHAZ as a miR-451 target gene. We next investigated the effects of YWHAZ knockdown on osteoblastic differentiation. To examine the effects of miR-451's antagomir in vivo, we injected ovariectomized (OVX) or sham-operated mice with miR-451's antagomir over a period of six weeks. We isolated stromal cells from murine bone marrow on week six for further ex vivo experimentation. Results: miR-451's antagomir...Continue Reading

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Citations

Jan 30, 2020·Frontiers in Pharmacology·Xin YanJia-Kuo Yu
Apr 10, 2019·International Journal of Endocrinology·Xi SunXianghang Luo
May 21, 2019·Journal of Cellular Biochemistry·Lujun Li, Dianming Jiang
Sep 22, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiang-Dong LuYan-Xiong Liu
Nov 22, 2020·Bone·Austin P Hensley, Audrey McAlinden
Jul 27, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardMohammad Samadian

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Methods Mentioned

BETA
transfection
light microscopy
PCR
transfections
Protein Assay
electrophoresis
fluorescence imaging

Software Mentioned

TargetScan
Leica
Qwin
GenePix Pro
Image Lab
SPSS
miRanda

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