# The Role of MicroRNA in Osteoarthritis: Alzheimer's Administrative Supplement

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $392,500

## Abstract

Project Summary
Alzheimer’s disease (AD) is one of the most common aging-related diseases, affecting more than 5.5 million
Americans age 65 and older and thus creating enormous socioeconomic burden. To date there is no cure for
AD, due to our limited understanding of AD and biological processes of aging. We have found that two
homologous miRNAs, miR-204 and miR-211, are essential for aged joint cells to maintain healthy homeostasis
to counteract osteoarthritis (OA) pathogenesis. Interestingly, the mouse model with double knockout (dKO) of
miR-204 and miR-211 displayed multiple pathological changes, mostly aging-related, such as OA in joints,
hypermature cataracts with rupture, uveal melanosis, and retinal dysplasia in eyes, follicular dysplasia in skins,
and valvular endocardiosis in hearts. Particularly, accelerated aging appears to occur in the brain of the dKO
mice. Thus, the dKO mice may represent a unique, comprehensive model of aging. Deep sequencing of
miRNAs has demonstrated that miR-204 is dominantly expressed in brain, and bioinformatic analysis reveals
that multiple AD-associated genes may be targeted by miR-204/-211. In consideration of multiplexed aging
phenotypes in the dKO mice, we hypothesize that miR-204 and miR-211 play important roles in brain
pathophysiology and miR-204/-211 loss-of-function may exacerbate the pathogenesis of AD. Thus, we
propose two Specific Aims in this supplement to expand our study of miRNA role in OA on AD, both diseases
involving dysregulation of biological processes of aging. In Aim 1, we will identify AD-associated genes
targeted by miR-204/-211 in brain cells, and in Aim 2, we will determine if miR-204/-211 loss-of-function
exacerbates AD pathogenesis in a mouse model of AD. New insights uncovered from this study will deepen
our understanding of AD and shed light into how accelerated aging occurs, thus advancing the development of
innovative therapeutic options to treat numerous aging-related disorders including AD and OA.

## Key facts

- **NIH application ID:** 10287295
- **Project number:** 3R01AR070222-04S1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jian Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,500
- **Award type:** 3
- **Project period:** 2017-08-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287295

## Citation

> US National Institutes of Health, RePORTER application 10287295, The Role of MicroRNA in Osteoarthritis: Alzheimer's Administrative Supplement (3R01AR070222-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10287295. Licensed CC0.

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