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Updated: Feb 16, 2026
The Generation of Closed Femoral Fractures in Mice: A Model to Study Bone Healing
Published on: August 16, 2018
The Effects of Systemic Therapy of PEGylated NEL-Like Protein 1 (NELL-1) on Fracture Healing in Mice
Justine Tanjaya1, Elizabeth L Lord2, Chenchao Wang3
1Division of Growth and Development and the Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Abstract:
Fractures are common, with an incidence of 13.7 per 1000 adults annually. Systemic agents have been widely used for enhancing bone regeneration; however, the efficacy of these therapeutics for the management and prevention of fracture remains unclear. NEL-like protein 1 (NELL-1) is a potent pro-osteogenic cytokine that has been modified with polyethylene glycol (PEG)ylation [PEGylated NELL-1 (NELL-PEG)] to enhance its pharmacokinetics for systemic therapy. Our aim was to investigate the effects of systemic administration of NELL-PEG on fracture healing in mice and on overall bone properties in uninjured bones. Ten-week-old CD-1 mice were subjected to an open osteotomy of bilateral radii and treated with weekly injections of NELL-PEG or PEG phosphate-buffered saline as control. Systemic injection of NELL-PEG resulted in improved bone mineral density of the fracture site and accelerated callus union. After 4 weeks of treatment, mice treated with NELL-PEG exhibited substantially enhanced callus volume, callus mineralization, and biomechanical properties. NELL-PEG injection significantly augmented bone regeneration, as confirmed by high expression of bone turnover rate, bone formation rate, and mineral apposition rate. Consistently, the immunohistochemistry results also confirmed a high bone remodeling activity in the NELL-PEG-treated group. Our findings suggest that weekly injection of NELL-PEG may have the clinical potential to accelerate fracture union and enhance overall bone properties, which may help prevent subsequent fractures.
Insights
Systemic administration of PEGylated NEL-like protein 1 (NELL-PEG) significantly accelerates fracture healing in mice. This novel therapy enhances bone regeneration and improves bone properties, potentially preventing future fractures.
Area of Science:
- Orthopedics
- Biomaterials Science
- Regenerative Medicine
Background:
- Fractures are a common orthopedic issue, with limited systemic therapeutic options for enhancing bone regeneration.
- NEL-like protein 1 (NELL-1) is a pro-osteogenic cytokine, modified via polyethylene glycol (PEG)ylation to create NELL-PEG for improved systemic delivery and pharmacokinetics.
Purpose of the Study:
- To evaluate the efficacy of systemically administered NELL-PEG in promoting fracture healing and improving bone properties in a murine model.
Main Methods:
- An open osteotomy model was used in CD-1 mice, with weekly systemic injections of NELL-PEG or a control solution.
- Fracture healing, bone mineral density, callus formation, mineralization, biomechanical properties, and bone turnover markers were assessed.
Main Results:
- NELL-PEG treatment significantly accelerated callus union and improved bone mineral density at the fracture site.
- Enhanced callus volume, mineralization, and biomechanical strength were observed in NELL-PEG treated mice after 4 weeks.
- Bone regeneration markers, including bone turnover rate, bone formation rate, and mineral apposition rate, were significantly augmented.
Conclusions:
- Systemic administration of NELL-PEG demonstrates potent osteogenic effects, accelerating fracture healing and enhancing overall bone quality.
- These findings suggest NELL-PEG holds clinical potential for fracture management and prevention of subsequent fractures.
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