# Trafficking and translation of mRNA in osteocyte dendrites

> **NIH NIH F32** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $67,582

## Abstract

Project Summary
 Osteocytes form an interconnected network within bone by extending long dendritic projections that
connect to each other, to the vasculature, and to cells on the bone surface. Proper formation and maintenance
of these dendrites are critical for osteocyte viability and for osteocytic maintenance of the surrounding bone.
During aging and in many bone diseases, loss of osteocyte dendrites precedes osteocyte death and bone
fragility. However, we do not fully understand the mechanisms by which osteocytes form and maintain their
dendrites. We will take an innovative approach to improve understanding of osteocyte dendrite biology by
studying molecular mechanisms known to act in projections of other cells like neurons. Specifically, we will
examine the ability of osteocytes to traffic mRNA to their dendritic projections and locally translate proteins. Since
we have already demonstrated robust dendrite enrichment of over 400 mRNA transcripts, our rationale is that
osteocyte projections may share a common molecular regulatory mechanism with projections of other cell types
to regulate the local transcriptome, proteome, and function of this subcellular compartment. Mis-localization of
mRNA has been implicated in a wide range of disorders from neurodegenerative disease to cancer, but is
completely unexplored in osteocytes. Therefore, the proposed research is significant because it will advance
understanding of molecular cell biology in osteocytes, and it may provide new targets for therapies to treat bone
disease and improve bone fragility. We will test the hypothesis that osteocytes translate dendrite-enriched
mRNAs locally in dendrites, and that mRNAs are trafficked to dendrites via ‘zip code’ sequences in their 3’
untranslated region (3’UTR). In our first specific aim we will validate localization of top dendrite-enriched
transcripts in vivo using in situ hybridization in bone, and then we will demonstrate local translation of osteocyte
dendrite-enriched mRNAs using translational profiling and puromycin incorporation assays. We expect that
dendrite-localized transcripts encode proteins that play essential roles in the function of osteocyte dendrites and
will therefore be locally translated. In our second specific aim, we will identify ‘zip code’ localization sequences
in dendrite-enriched transcripts and RNA binding proteins that confer dendrite localization in osteocytes using a
heterologous reporter assay and then affinity purification with mass spectrometry. We expect that a fragment
within the 3’UTR of each dendrite-enriched transcript will serve as the binding site for an RNA binding protein
that trafficks that transcript to dendrites. The long-term goal of this work is to elucidate the contribution of
dendrite-localized mRNAs to formation and function of osteocyte dendrites, including the role of specific RNA
binding proteins and regulation of local translational activity. Together, this work will characterize a molecular
mechanism t...

## Key facts

- **NIH application ID:** 10535515
- **Project number:** 1F32AR081660-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Courtney Marisa Mazur
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2022-11-15 → 2024-02-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535515

## Citation

> US National Institutes of Health, RePORTER application 10535515, Trafficking and translation of mRNA in osteocyte dendrites (1F32AR081660-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10535515. Licensed CC0.

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