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LncRNA ENST00000563492 promoting the osteogenesis-angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by functions as a ceRNA for miR-205-5p.

ABSTRACT: Pain, physical dysfunction, and mental disorders caused by bone nonunion bring great burden to patients. Bone mesenchymal stem cells (BMSCs) isolated from bone nonunion patients with poor proliferation and osteogenic ability are compared with that from normal bone-healing patients. Long noncoding RNAs (lncRNAs) are a class of RNAs that are more than 200 nucleotides in length, lack an open-reading frame encoding a protein, and have little or no protein-coding function, and could regulate gene expression, which is involved in the regulation of important life activities, such as growth, development, aging, and death at epigenetic, transcriptional, and post-transcriptional levels. In this study, we intended to investigate the difference of lncRNA expression between patients with nonunion and normal fracture healing. Our result found that lncRNA ENST00000563492 was downregulated in bone nonunion tissues. LncRNA ENST00000563492 promotes osteogenic differentiation of BMSCs through upregulating the expression of CDH11. On the other hand, LncRNA ENST0000563492 could improve the osteogenesis-angiogenesis coupling process through enhancing the expression of VEGF during osteogenic differentiation of BMSCs. LncRNA ENST00000563492 functions as a ceRNA for miR-205-5p that was targeting CDH11 and VEGF. LncRNA ENST00000563492 could promote the osteogenesis of BMSCs in vivo. Our result indicated that lncRNA ENST00000563492 may be a new target for bone nonunion.

SUBMITTER: Ouyang Z

PROVIDER: S-EPMC7316863 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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LncRNA ENST00000563492 promoting the osteogenesis-angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by functions as a ceRNA for miR-205-5p.

Ouyang Zhengxiao Z Tan Tingting T Zhang Xianghong X Wan Jia J Zhou Yanling Y Jiang Guangyao G Yang Daishui D Liu Tang T

Cell death & disease 20200625 6

Pain, physical dysfunction, and mental disorders caused by bone nonunion bring great burden to patients. Bone mesenchymal stem cells (BMSCs) isolated from bone nonunion patients with poor proliferation and osteogenic ability are compared with that from normal bone-healing patients. Long noncoding RNAs (lncRNAs) are a class of RNAs that are more than 200 nucleotides in length, lack an open-reading frame encoding a protein, and have little or no protein-coding function, and could regulate gene exp ...[more]

PMID: 32587236

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Project description:BackgroundBone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown.MethodsMouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed.ResultsLLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β.ConclusionsLLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.

Dataset Information

LncRNA ENST00000563492 promoting the osteogenesis-angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by functions as a ceRNA for miR-205-5p.

Publications

LncRNA ENST00000563492 promoting the osteogenesis-angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by functions as a ceRNA for miR-205-5p.

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