# The role of NF-kB in mesenchymal stem cells during diabetic wound healing

> **NIH NIH K08** · UNIVERSITY OF PENNSYLVANIA · 2021 · $133,272

## Abstract

Project summary/abstract.
Dr. Ko is enrolled in a uniquely combined periodontics and Doctor of Science in Dentistry (DScD) program at
the University of Pennsylvania School of Dental Medicine. Under the mentorship of Dr. Dana Graves and the
thesis committee, Dr. Ko will investigate the effect of diabetes on mesenchymal stem cells (MSCs) during hard
and soft tissue wound healing. This topic of interest is important in the field of periodontology as wound
healing of the hard and soft tissue is a critical component of numerous periodontal diseases that are often
exacerbated by diabetes. Dr. Ko is committed to a career in academics, which will be greatly enhanced by the
educational, technical and career development trainings afforded by the K08 Award. The established
specialty/DScD program at Penn will serve as an important step stone for Dr. Ko's long term goal to eventually
emerge as an independent researcher, studying how systemic disease alters local stem cell behavior in the oral
cavity. Diabetes delays hard and soft tissue wound healing through persistent inflammation. How diabetes
leads to greater inflammation in the healing environment remains largely unknown. Recent advances in
transplantation studies have demonstrated that MSCs play an essential anti-inflammatory role. Diabetes may
interfere with their anti-inflammatory function to enhance the inflammatory environment. Prolonged
activation of nuclear-factor kappa B (NF-κB), a master inflammatory transcription factor, has been implicated
in diabetic complications. We propose that NF-κB is activated by the diabetic conditions in MSCs and
contributes to impaired diabetic soft and hard tissue wound healing. To address this issue, we generated mice
that have lineage specific deletion of IKK-beta in MSCs, a kinase essential for activation of NF-κB. Our
preliminary data demonstrate that conditional deletion of IKK-beta in MSCs increases the number of MSCs,
reduces the level of inflammation and improves the outcome in fracture healing in diabetic animals, suggesting
a negative role of NF-κB in these cells in diabetic healing. Thus, we propose a central hypothesis that activation
of NF-κB in MSCs in diabetic conditions negatively affects hard and soft tissue healing by reducing the number
of MSCs and by interfering with the anti-inflammatory function of MSCs. Aim 1 will establish the important
role of intrinsic NF-κB in regulating MSC number and function during fracture and gingival wound healing
under diabetic condition. Aim 2 will investigate whether diabetes alters regulation of genes associated with
delayed healing, and determine if this is reversed by inhibiting NF-κB activation in MSCs. Aim 3 will determine
whether NF-κB inhibitor is a novel treatment for diabetic fracture and gingival wound healing by improving
MSC activities. Collectively, these studies will further our understanding of mechanism underlying diabetic
complications in hard and soft tissue wound healing. Successful completion of...

## Key facts

- **NIH application ID:** 10169406
- **Project number:** 5K08DE027129-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** KANG I KO
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $133,272
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169406

## Citation

> US National Institutes of Health, RePORTER application 10169406, The role of NF-kB in mesenchymal stem cells during diabetic wound healing (5K08DE027129-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10169406. Licensed CC0.

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