# Magnesium and Arthritis Pathogenesis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $372,900

## Abstract

ABSTRACT
Rheumatoid arthritis (RA) is a common and chronic autoimmune arthritis that causes erosive joint damage
and deformities, with increased risk for disability and reduced life expectancy. Recent new therapies have
significantly improved disease control but remission remains uncommon and new and better treatments are
needed. We have recently discovered a previously unrecognized role for magnesium in the regulation of
arthritis. Specifically, a short-term experimental low magnesium diet was highly protective reducing arthritis
severity and histologic joint damage in pristane-induced arthritis (PIA) in rats and collagen-induced arthritis
(CIA) in mice, two well-established models or RA. Our observations suggest that the arthritis-protective
effect involves a magnesium-dependent interference with Treg, Tr1 or Th17 cell development and/or
localization to the joint. The specific aims are: AIM 1. To determine the role of magnesium on Treg, Tr1
and Th17 T cell differentiation and in fibroblast-like synoviocytes (FLS). Subaim 1. To characterize the
effect of reduced magnesium conditions on in vitro Treg, Tr1 and Th17 T cell differentiation and function.
Subaim 2. To determine the role of specific magnesium channels in Treg, Tr1 and Th17 differentiation. The
role of specific magnesium channels on in vitro Treg, Tr1 and Th17 differentiation will be examined in
experiments with siRNA knock-down, and with antagonists and agonists. Subaim 3. The role of magnesium
in fibroblast-like synoviocyte (FLS) production of of pro-inflammatory mediators. We will examine whether
low concentrations of magnesium reduce the RA FLS production of inflammatory factors including those
required for the influx of Th17 and other cells into the synovial tissues, and whether a specific magnesium
channel accounts for that. AIM 2. In vivo effect of a short-term experimental low magnesium diet on
established arthritis, on the development of protective and pathogenic T cell subsets, and on the
intestinal microbiome. Subaim 1. To determine the effect of a short-term low magnesium diet initiated
after the onset of disease on arthritis severity and joint damage. It is hypothesized that a low-magnesium
diet initiated after the onset of arthritis (CIA) will significantly reduce disease severity and histologic joint
damage. The role of specific magnesium channels will be examined with inhibitors. Subaim 2. To determine
the role of reduced magnesium conditions on Treg, Tr1 and Th17 cell differentiation in vivo. Will examine
the effect of low and high magnesium diets on the numbers of Treg, Tr1 and Th17 cells in arthritis induced
in mice with inducible IL17-eGFP/Foxp3-mRFP. Submaim 3. Effect of reduced magnesium conditions on
the gut microbiome. We have hypothesized that the low magnesium diet protective effect could be related to
changes induced by the diet in the gut microbiome and will comprehensively examine that.

## Key facts

- **NIH application ID:** 9850515
- **Project number:** 5R01AR073165-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Percio S Gulko
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $372,900
- **Award type:** 5
- **Project period:** 2019-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850515

## Citation

> US National Institutes of Health, RePORTER application 9850515, Magnesium and Arthritis Pathogenesis (5R01AR073165-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9850515. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*