# The epigenetic role of LSD1 in osteoclast differentiation

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2022 · $52,552

## Abstract

PROJECT SUMMARY
Diseases such as osteoporosis and periodontal disease affect millions of individuals annually in the United
States and cost billions in treatment. Osteoclasts are large, multinucleated cells that secrete acid and
proteases to resorb bone. Understanding the molecular mechanisms that regulate osteoclast differentiation
and activity will provide insight as to how the hyper-active osteoclasts causing pathological bone loss,
contributes to osteoporosis and periodontal disease. Reversible modifications to DNA such as histone
acetylation, methylation, phosphorylation and ubiquitylation alter the access of transcriptional machinery to
DNA and regulate gene expression. Lysine-specific demethylase 1 (LSD1), also known as KDM1A, is the first
identified histone demethylase capable of specially demethylating mono- and di-methylated lysine 4 of histone
3 (H3K4me1/2) or lysine 9 of histone 3 (H3K9me1/2). LSD1 confers transcriptional repression by
demethylating H3K4 or activating transcription by demethylating H3K9. The mechanism by which LSD1
regulates osteoclast gene expression and differentiation is currently unknown. Preliminary data presented in
this proposal demonstrate inhibition of LSD1 activity or expression leads to an increase in mono-methylation of
H3K4me1 and an increase in osteoclast differentiation. These preliminary data suggest LSD1 is a repressor of
osteoclast gene expression. This proposal aims to characterize the role of LSD1 in regulating osteoclast
differentiation in both an animal model and as well as in an in vitro cell culture model (Aim 1) and identifying
the osteoclast genes that are regulated by LSD1 (Aim 2). These research goals will be enhanced by the
training goals of the application. These training goals include learning techniques such as micro-CT, RNA-SEQ
and ChIP-SEQ as well as participation in journal clubs and local and national scientific meetings. Training
takes place at the University of Minnesota which offers an outstanding environment for both research and
clinical dental training.

## Key facts

- **NIH application ID:** 10452704
- **Project number:** 5F30DE030354-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** KRISTINA ASTLEFORD-HOPPER
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $52,552
- **Award type:** 5
- **Project period:** 2020-08-29 → 2024-08-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452704

## Citation

> US National Institutes of Health, RePORTER application 10452704, The epigenetic role of LSD1 in osteoclast differentiation (5F30DE030354-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10452704. Licensed CC0.

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