MiR-497∼195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1α activity

Autor: Hui Peng, Hong-Bo He, Tian Su, Man Li Tu, Tie Jian Jiang, Qi Guo, Mei Wan, Mi Yang, Xiang Hang Luo, Qiong Lu, Qing Liu, Ye Xiao, Changjun Li, Xi Sun, Xu Cao, Min Xiang Lei
Rok vydání: 2017
Předmět:
0301 basic medicine
CD31
medicine.medical_specialty
F-Box-WD Repeat-Containing Protein 7
Bone density
Endothelium
Angiogenesis
Sialoglycoproteins
Science
Transgene
Neovascularization
Physiologic
General Physics and Astronomy
Biology
Bone and Bones
Prolyl Hydroxylases
Article
General Biochemistry
Genetics and Molecular Biology
Neovascularization
Mice
03 medical and health sciences
Bone Density
Osteogenesis
Internal medicine
medicine
Animals
Humans
Molecular Targeted Therapy
Receptor
Notch1
Receptor
Mice
Knockout
Multidisciplinary
Antagomirs
Gene Expression Regulation
Developmental
General Chemistry
Aptamers
Nucleotide
Hypoxia-Inducible Factor 1
alpha Subunit
Cell biology
Platelet Endothelial Cell Adhesion Molecule-1
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Endocrinology
cardiovascular system
Osteoporosis
Signal transduction
medicine.symptom
Signal Transduction
Zdroj: Nature Communications, Vol 8, Iss 1, Pp 1-11 (2017)
Nature Communications
ISSN: 2041-1723
DOI: 10.1038/ncomms16003
Popis: A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31hiEmcnhi), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31hiEmcnhi vessels decrease during ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31hiEmcnhi endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31hiEmcnhi vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31hiEmcnhi vessels and bone loss. miR-497∼195 cluster maintains the endothelial Notch activity and HIF-1α stability via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium-specific activation of miR-195 by intravenous injection of aptamer-agomiR-195 stimulates CD31hiEmcnhi vessel and bone formation in aged mice. Together, our study indicates that miR-497∼195 regulates angiogenesis coupled with osteogenesis and may represent a potential therapeutic target for age-related osteoporosis.
H-type endothelium, defined by the high expression of CD31 and endomucin, is found in the bone where it promotes angiogenesis and osteogensis. Here Yang et al. show that the miR-497∼195 cluster regulates the generation and maintenance of the H-type endothelium by controlling the levels of Notch regulator Fbxw7 and the HIF regulator P4HTM.
Databáze: OpenAIRE
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