# The essential role of miR-27a in craniofacial and body skeletons

> **NIH NIH R21** · ADA FORSYTH INSTITUTE, INC. · 2020 · $40,475

## Abstract

Abstract
MicroRNAs are ~22 nucleotides noncoding RNAs which control gene expression at post-transcriptional levels.
Owing to its ability to simultaneously modulate a vast amount of genes, microRNA has been postulated to
workas a master regulator for cell type-specific development and function. Although gain-of-function analysis
with microRNA overexpression can affect these processes in transgenic mice, loss-of-function study often
fails to detect phenotypic alterations and is unable to faithfully determine their role in development and
disease. Moreover, results obtained from in vitro analysis sometimes are not supported by functional analyses
in vivo. Studies of Dicer, an enzyme essential for biosynthesis of microRNAs, have implicated their importance
in boneremodeling. However, the exact miRNA(s) involved has not been identified. The cluster of miR-
23a~27a~24-2 consists of three miRNAs generated from a single transcript. Dysregulation of miR-23a and
miR-27a has beenshown in osteoporosis patients but their regulatory role remains elusive. In cell culture
study, high levels of miR-23a or miR-27a inhibits OB differentiation, suggesting that they are negative
regulators for bone formation.In mice, OB-specific expression of miR-23a~27a~24-2 cluster reveals its effects
on osteocyte but not OB differentiation. The animal study does not support the cell culture analysis. There is
an urgent need to develop loss-of-function models to definitively assess the function of these microRNAs in
vivo. To fill our knowledge gaps, we created a mouse model deficient for miR-27a using CRSPR-Cas9 gene
editing. The loss of this single miRNA causes severe osteoporosis in the craniofacial and body skeletons,
suggesting the function of miR-27a cannot be substituted. The bone loss phenotype also becomes more
prominent with age. New genetic evidence, indicating miR-27a as a positive regulator in bone remodeling,
strongly argues against the previous cell culture study. In this application, we will characterize craniofacial and
skeletal defects in miR-27adeficient mice. We will examine osteoblast and osteoclast abnormalities associated
with the mutation to causean imbalance in skeletal remodeling. To further elucidate the mechanism by which
miR-27a regulates bone formation and resorption, we will identify its direct targets using unbiased screening.
The completion of this proposal has outstanding potential to advance our knowledge base of epigenetic
regulation in bone metabolism, leading to novel strategies for prevention and treatment of craniofacial and
skeletal disorders.

## Key facts

- **NIH application ID:** 10433673
- **Project number:** 7R21DE028696-03
- **Recipient organization:** ADA FORSYTH INSTITUTE, INC.
- **Principal Investigator:** Takamitsu Maruyama
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,475
- **Award type:** 7
- **Project period:** 2021-06-17 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433673

## Citation

> US National Institutes of Health, RePORTER application 10433673, The essential role of miR-27a in craniofacial and body skeletons (7R21DE028696-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10433673. Licensed CC0.

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