Silencing long non‐coding RNA MEG3 accelerates tibia fraction healing by regulating the Wnt/β‐catenin signalling pathway

As fracture healing is related to gene expression, fracture healing is prospected to be implicated in long non‐coding RNAs (lncRNAs). This study focuses on the effects of epigenetic silencing of long non‐coding RNA maternally expressed gene 3 (lncRNA MEG3) on fracture healing by regulating the Wnt/β...

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Published in:Journal of cellular and molecular medicine 2019-06, Vol.23 (6), p.3855-3866
Main Authors: Liu, Yu‐Bao, Lin, Lu‐Pan, Zou, Rui, Zhao, Qing‐Hua, Lin, Fu‐Qing
Format: Article
Language:English
Subjects:
Animals
beta Catenin - metabolism
Bony Callus - metabolism
Collagen Type II - metabolism
Core Binding Factor Alpha 1 Subunit - metabolism
Disease Models, Animal
Down-Regulation
fracture healing
Fracture Healing - genetics
Fracture Healing - physiology
Gene Silencing
Glycogen Synthase Kinase 3 beta - chemistry
Glycogen Synthase Kinase 3 beta - genetics
Glycogen Synthase Kinase 3 beta - metabolism
long non‐coding RNA
maternally expressed gene 3
Mice
Mice, Inbred C57BL
Mice, Transgenic
Original
Osteocalcin - metabolism
RNA Interference
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Sp7 Transcription Factor - metabolism
Tibia fracture
Tibial Fractures - genetics
Tibial Fractures - metabolism
Tissue Array Analysis
Up-Regulation
Wnt Signaling Pathway - genetics
Wnt/β‐catenin signal pathway
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Summary:As fracture healing is related to gene expression, fracture healing is prospected to be implicated in long non‐coding RNAs (lncRNAs). This study focuses on the effects of epigenetic silencing of long non‐coding RNA maternally expressed gene 3 (lncRNA MEG3) on fracture healing by regulating the Wnt/β‐catenin signalling pathway. Genes expressed in fracture were screened using bioinformatics and the subcellular location of MEG3 was determined using FISH. Next, we successfully established tibia fracture (TF) models of C57BL/6J and Col2a1‐ICAT mice and the effect of silencing lncRNA MEG3 on fracture healing was detected after TF mice were treated with phosphate buffer saline (PBS), MEG3 siRNA and scramble siRNA. X‐ray imaging, Safranin‐O/fast green and haematoxylin‐eosin (HE) staining and histomorphometrical and biomechanical analysis were adopted to observe and to detect the fracture healing conditions. Additionally, the positive expression of collagen II and osteocalcin was examined using immunohistochemistry. At last, in the in vitro experiment, the relationship of MEG3 and the Wnt/β‐catenin signalling pathway in fraction healing was investigated. MEG3 was located in the cell nucleus. In addition, it was found that MEG3 and the Wnt/β‐catenin signalling pathway were associated with fraction healing. Moreover, silencing MEG3 was proved to elevate callus area and maximum bending load and to furthermore enhance the recanalization of bone marrow cavity. Finally, MEG3 knockdown elevated levels of Col10a1, Runx2, Osterix, Osteocalcin, Wnt10b and β‐catenin/β‐catenin whereas it reduced p‐GSK‐3β/GSK‐3β levels. Taken together, our data supported that epigenetic silencing of lncRNA MEG3 could promote the tibia fracture healing by activating the Wnt/β‐catenin signalling pathway.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.14229