# PGC-1a regulates inflammation and bone loss in periodontitis through NF-kB

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $447,963

## Abstract

Abstract
Periodontal disease or periodontitis is characterized with inflammation and bone loss due to oral infection.
Importantly, growing evidence suggests that chronic periodontal inflammation is an important risk factor for
diabetes, heart diseases, oral cancer, and other systemic diseases. Increased periodontitis is associated with
aging, and it represents a significant public concern in the aging population. The mouse model of periodontitis
suggests that aging promotes microbial colonization, disease susceptibility, periodontal inflammation and bone
loss. However, how aging affects the onset and progression of periodontitis is not fully understood. Peroxisome
proliferator-activated receptor γ coactivators 1α (PGC-1α; encoded by Ppargc1α, also known as Pgc-1α) is a
master regulator of mitochondrial biogenesis and oxidative metabolism in skeletal muscle, liver, brain and the
heart. PGC-1α has been shown to interplay with the NF-κB pathway in skeletal muscle and cardiac cells.
During the last funding period, we showed that the immune transcription factor nuclear factor kappa B (NF-κB)
played a critical role in bone loss of periodontitis and osteoporosis. Although it is well known that loss of PGC-
1α is associated with increased ROS, aging and chronic inflammation, its role in periodontal inflammation and
bone homeostasis is largely unexplored. Therefore, we explored the role of PGC-1α in periodontitis and
osteoporotic bone loss. Unexpectedly, we found that PGC-1α was abundantly expressed in monocytes and
macrophages, but its expression levels were downregulated with aging. Importantly, genetic studies revealed
that loss of PGC-1α significantly increased periodontal inflammation and alveolar bone loss induced by oral
infection. Additionally, we found that loss of PGC-1α intrinsically enhanced the expression of pro-inflammatory
cytokines in macrophages and osteoclastogenesis by enhancing NF-κB activation in vitro. Based on these
exciting novel discoveries, in this competing renewal, we hypothesize that PGC-1α plays a critical role in
control of periodontal inflammation and alveolar bone loss in periodontitis by inhibiting NF-κB. Loss of PGC-1α
not only promotes the expression of inflammatory mediators, but also enhances osteoclastogenesis and bone
resorption. To test our hypothesis, we propose the following three specific aims: 1) Determine whether loss of
PGC-1α in monocytes/macrophages exacerbates periodontal inflammation and alveolar bone loss in
periodontitis by enhancing NF-κB; 2) Determine if induction of PGC-1α can attenuate periodontal inflammation
and alveolar bone loss in periodontitis by inhibiting NF-κB; and 3) Explore the molecular mechanisms by which
PGC-1α regulates periodontal inflammation and osteoclastogenesis through NF-κB. New findings from our
studies may identify a novel factor that regulates periodontal inflammation and bone loss in periodontitis, and
have important implications in the prevention and treatment of periodont...

## Key facts

- **NIH application ID:** 10129343
- **Project number:** 5R01DE019412-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** CUN-YU WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $447,963
- **Award type:** 5
- **Project period:** 2008-09-08 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129343

## Citation

> US National Institutes of Health, RePORTER application 10129343, PGC-1a regulates inflammation and bone loss in periodontitis through NF-kB (5R01DE019412-14). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10129343. Licensed CC0.

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