# microRNA regulation of osteocyte metabolism in bone remodeling

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $52,552

## Abstract

Matrix turnover in bone occurs through bone remodeling and is essential to maintaining bone homeostasis and
health. Osteocytes, which are cells embedded in the bone matrix, regulate bone remodeling both directly by
controlling the activity of osteoblasts and osteoclasts and indirectly through perilacunar/canalicular remodeling
(PLR). The ability of osteocytes to regulate osteoblast and osteoclast activity in bone remodeling and
homeostasis is well known, but many questions remain about the direct role of osteocyte in remodeling via
PLR in bone homeostasis or disease states. In PLR, osteocytes directly resorb and deposit bone matrix
surrounding their lacuno-canalicular network (LCN). Indeed, osteocyte-intrinsic deletion of TGFβ signaling in
TβRIIocy−/− mice causes defective PLR and bone quality. Furthermore, preliminary data from RNAseq of
TβRIIocy−/− bone shows significant mitochondrial dysfunction. However, the underlying molecular mechanism of
how TGFβ regulates mitochondrial function and PLR in osteocytes is currently poorly understood.
One of the most well-known molecular regulators of mitochondrial function and metabolism in other cell/tissue
types is microRNAs (miRs). miRs are endogenous, small non-coding RNAs that facilitate sequence-dependent
post-transcriptional gene regulation and coordinately target gene networks of complex biological processes,
such as cellular metabolism. However, the role of miRs in mediating osteocyte mitochondrial function has not
been explored.
This project will test the hypothesis that osteocytic TGFβ signaling regulates mitochondrial function via
a miRNA-dependent mechanism to control osteocyte function by focusing on a microRNA cluster, miR-181a/b. Aim 1 will determine the requirement of miR-181a/b for osteocyte function. Aim 2 will determine the
extent to which miR-181a/b regulate mitochondrial function in osteocytes. Aim 3 will determine whether the
regulation of mitochondrial function by TGFβ is miR-181a/b-dependent. This study will aid our understanding of
mechanisms responsible for maintaining homeostatic PLR and potentially aid in the development of new,
innovative approaches to treat or prevent bone diseases, including in the craniofacial skeleton, due to bone
remodeling defects.

## Key facts

- **NIH application ID:** 10403427
- **Project number:** 5F30DE029986-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jihee Yoon
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $52,552
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403427

## Citation

> US National Institutes of Health, RePORTER application 10403427, microRNA regulation of osteocyte metabolism in bone remodeling (5F30DE029986-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10403427. Licensed CC0.

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