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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-143 promotes angiogenesis and osteoblast differentiation by targeting HDAC7
Renkai Wang1,2, Hao Zhang1, Wenbin Ding1
1Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai, China.
Abstract:
The regulation of bone formation and detailed mechanisms are still largely elusive, and the roles of microRNAs in this process have attracted much attention. Recently, a specific subtype of CD31hiendomucinhi (CD31hiEMCNhi) endothelium has been identified to promote bone formation, together with osteoblast development. However, the role of microRNA143 in the generation of CD31hi EMCNhi endothelium and bone formation remains unknown. In this study, we found that miR-143 was expressed both in osteoblast cells and CD31hiEMCNhi endothelial cells. Serum miR-143 level was negatively correlated with age in humans. Overexpression of miR-143 promoted osteoblast formation and angiogenic effects. Furthermore, CD31hiEmcnhi vessels and osteoblast formation were significantly inhibited in miR-143 knockout mice. Mechanistically, inhibitor HDAC7 was directly targeted by miR-143 and knockdown of HDAC7 was found to rescue the function of miR-143 deficiency. Thus, miR-143 promotes angiogenesis coupling with osteoblast differentiation by targeting HDAC7, which may serve as a potential target in angiogenic and osteogenic diseases.
Insights
MicroRNA-143 promotes bone formation and blood vessel growth by regulating CD31hiEMCNhi endothelium. It targets HDAC7, offering potential therapeutic strategies for bone and blood vessel diseases.
Area of Science:
- Biomedical research
- Molecular biology
- Vascular biology
Background:
- Bone formation regulation is complex and not fully understood.
- MicroRNAs are increasingly recognized for their roles in biological processes.
- A specific endothelium subtype (CD31hiEMCNhi) promotes bone formation and osteoblast development.
Purpose of the Study:
- To investigate the role of microRNA-143 (miR-143) in CD31hiEMCNhi endothelium generation.
- To determine the function of miR-143 in bone formation and angiogenesis.
- To elucidate the molecular mechanism by which miR-143 influences these processes.
Main Methods:
- Expression analysis of miR-143 in osteoblasts and CD31hiEMCNhi endothelial cells.
- Correlation analysis of serum miR-143 levels with age in humans.
- In vivo studies using miR-143 overexpression and knockout mouse models.
- Mechanistic studies involving target gene identification (HDAC7) and knockdown experiments.
Main Results:
- miR-143 is expressed in osteoblasts and CD31hiEMCNhi endothelial cells.
- Serum miR-143 levels decrease with age in humans.
- Overexpression of miR-143 enhances osteoblast formation and angiogenesis.
- miR-143 deficiency in mice impairs CD31hiEMCNhi vessel and osteoblast formation.
- miR-143 directly targets HDAC7, and its knockdown rescues miR-143 deficiency phenotypes.
Conclusions:
- miR-143 promotes angiogenesis coupled with osteoblast differentiation.
- The mechanism involves targeting HDAC7.
- miR-143 represents a potential therapeutic target for angiogenic and osteogenic diseases.
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