# Evaluation of pigment epithelium derived factor and its derived peptide for bone healing

> **NIH NIH R21** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $214,077

## Abstract

Abstract
The present exploratory application proposes to evaluate the use of two novel factors, Pigment epithelium
derived factor (PEDF) and a 17 amino acid peptide derived from it (P17) for the acceleration of healing femur
fractures created in serpinf1 knockout mice or wildtype mice. PEDF encoded by serpinf1 gene is synthesized
by a wide variety of cells in fetal and adult tissues. Mutations in serpinf1 gene cause type VI osteogenesis
imperfecta (OI) whose hallmark is excessive osteoid build up that fails to mineralize. Bone defects resulting
from trauma, bone tumors, and cranial facial defects may heal but a large number of them result in delayed
healing or nonunion. Autografts are usually used but there is a limited supply and tissue harvest may lead to
donor site morbidity. Allografts can be used but there is potential for disease transmission. Bone
morphogenetic proteins (BMPs) specifically, BMP-2 and BMP-7 have been approved for clinical use to
augment bone fracture healing. BMPs are very expensive, their mode of application remains problematic and
they are prone to inducing ectopic bone formation. We and others reported that PEDF promoted mesenchymal
stem cell (MSCs) differentiation and increased osteoblast mineralization and reduced expression of
Sost/Sclerostin by osteocytes. Preliminary data showed that P17, a peptide with affinity for PEDF-receptor
promoted osteoblast differentiation, increased matrix mineralization in vitro, and suppressed Sost expression
by osteocytes. P17 infused into serpinf1 knockout mice via the peritoneal cavity, increased stiffness of the
femurs which were reported to possess reduced stiffness. We are thus proposing to explore whether PEDF or
P17 possess ability to accelerate healing of delayed or nonunion bone fractures using two mice models. The
global hypothesize is PEDF or the P17 peptide will accelerate healing of critical sized mouse femoral defects
created in serpinf1 knockout mice or wildtype mice. PEDF possess antiangiogenic activity but the P17 peptide
does not, the peptide may possess superior ability to accelerate healing and regeneration of murine femoral
fractures. We will test the hypothesis through two aims. In aim 1, we will determine whether P17 or PEDF
delivered via the peritoneal cavity will accelerate healing of femur fractures created in serpinf1 knockout mice.
Critical sized fractures will be created in serpinf1 mice femurs; the mice will be injected with P17 or PEDF via
peritoneal cavity. Control mice will be injected with saline. Some mice will be followed by radiographic analysis
at weekly intervals to determine the extent of healing. At week 6, all mice will be sacrificed, femurs harvested
and evaluated by histology, micro CT and biomechanical testing. In aim 2, similar approaches will be carried
out but using wildtype mice. We predict that Both P17 and PEDF will accelerate healing of femur fractures in
both mice models but P17 may be more effective because it does not possess antian...

## Key facts

- **NIH application ID:** 9956083
- **Project number:** 1R21AR077199-01
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** CHRISTOPHER NIYIBIZI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $214,077
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9956083

## Citation

> US National Institutes of Health, RePORTER application 9956083, Evaluation of pigment epithelium derived factor and its derived peptide for bone healing (1R21AR077199-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9956083. Licensed CC0.

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