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

Mi Yang1,2, Chang-Jun Li1,2, Xi Sun1,3

  • 1Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.

Nature Communications
|July 8, 2017
PubMed

Insights

The miR-497∼195 cluster regulates bone vessel formation and bone mass by maintaining endothelial cell function. This microRNA cluster shows promise as a therapeutic target for age-related bone loss and osteoporosis.

Area of Science:

  • Vascular biology
  • Bone biology
  • Molecular genetics

Background:

  • A specific subtype of bone blood vessels (CD31hiEmcnhi) couples angiogenesis and osteogenesis.
  • The abundance of these vessels and the miR-497∼195 cluster expression decreases with age.

Purpose of the Study:

  • To investigate the role of the miR-497∼195 cluster in regulating age-related bone vascular changes and bone mass.
  • To explore the therapeutic potential of targeting this microRNA cluster for age-related osteoporosis.

Main Methods:

  • Analysis of miR-497∼195 expression in endothelial cells during aging.
  • Genetic manipulation of miR-497∼195 in mice (depletion and overexpression).
  • In vivo administration of agomiR-195 in aged mice.

Main Results:

  • miR-497∼195 depletion in endothelial cells reduced CD31hiEmcnhi vessels and bone mass.
  • Overexpression of miR-497∼195 in endothelium prevented age-related bone loss.
  • miR-497∼195 maintains endothelial Notch activity and HIF-1α stability by targeting Fbxw7 and P4HTM.
  • Intravenous injection of agomiR-195 stimulated bone and vessel formation in aged mice.

Conclusions:

  • The miR-497∼195 cluster is crucial for maintaining bone vascular integrity and bone mass during aging.
  • Targeting the miR-497∼195 cluster offers a potential therapeutic strategy for age-related osteoporosis.

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