# Project 2: Joint Transcriptomic and Epigenomic Studies for Male Osteoporosis

> **NIH NIH U19** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $225,345

## Abstract

Osteoporosis is the most common metabolic bone disease mainly characterized by low bone mineral density
(BMD,--areal BMD (aBMD) unless otherwise specified). Male osteoporosis is a major but most neglected public
health problem. Peripheral blood monocytes (PBMs) may act as precursors of osteoclasts, the bone resorption cells,
and produce cytokines important for osteoclast differentiation, activation, and apoptosis, and thus represent a major
systemic cell for bone metabolism. micro-RNA (miRNAs)-mediated gene expression modifications are important
transcriptomic dynamics underlying human diseases, and are involved in osteoclastogenesis in vitro. Next-G RNA-
seq has an unparalleled power to comprehensively characterize transcriptome, in particular, revealing novel
miRNAs. Therefore, our Hypothesis is: Changes in mRNA and miRNA expression profiles in PBMs underlie male
BMD and bone quality/strength variation and can be identified most powerfully by the cutting edge Next-G RNA-seq.
 Through the Clinical Core, we will recruit and clinically phenotype 200 Caucasian and 100 African American (AA)
men, aged 20-30, 150 (100 Caucasians and 50 AA) with high and 150 (100 Caucasians and 50 AA) with low BMD.
Bone quality/strength (measured by quantitative CT [QCT] and finite element analyses [FEA]) will also be assessed
on each subject. Half of the Caucasians (50 high vs. 50 low BMD subjects) will serve as a “discovery cohort” and the
other half as a “replication cohort”. These same subjects will all be used in Proj 2 & 3.
 In Aim 1, we will comprehensively identify mRNAs important to male osteoporosis. We will use the PBMs total
RNAs of the “discovery cohort” to perform RNA-seq-based transcriptome studies to identify mRNAs differentially
expressed (DEx) in high vs. low BMD subjects. We will identify the top 10 DEx genes and validate them in the
discovery cohort (within-cohort technical validation), the replication cohort (across-cohort biological validation), the
AA cohort (across-ethnicity validation), and another independent set of 86 Caucasian female (46 high vs. 40 low
BMD) subjects (from our SCOR, for across-sex validation). In silico replication in subjects of different sexes and/or
ethnicities will be performed in existing functional genomics datasets.
 In Aim 2, we will identify/validate DEx miRNAs in high vs. low BMD subjects and the target genes of the top DEx
miRNAs. We will identify the top 15 DEx miRNAs, and for each of which, identify top 5 potential target mRNAs
through correlation and bioinformatics analyses and also validate their “targeting” relationship in the above
mentioned cohorts/datasets as well as using luciferase-based functional assays.
 The significant mRNA/miRNA identified above will be tested for their significance for QTC and FEA measures.
 The data generated in this project will be used for more advanced analyses, such as eQTL/mQTL analyses,
gene network analyses, causality analyses and other integrative analyses , e.g., to 1) ga...

## Key facts

- **NIH application ID:** 10180819
- **Project number:** 5U19AG055373-05
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** ERIK K FLEMINGTON
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,345
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180819

## Citation

> US National Institutes of Health, RePORTER application 10180819, Project 2: Joint Transcriptomic and Epigenomic Studies for Male Osteoporosis (5U19AG055373-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10180819. Licensed CC0.

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