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Updated: Jan 8, 2026
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The Generation of Closed Femoral Fractures in Mice: A Model to Study Bone Healing
Published on: August 16, 2018
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Delayed Bone Fracture Healing in Hybid (Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization)-Deficient
Suguru Wakana1, Takako Negishi-Koga2, Masahiro Momoeda3
1Department of Pathophysiology for Locomotive Diseases, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan.
The American Journal of Pathology
|December 15, 2025
Summary
Hyaluronan (HA)-binding protein (HYBID) deficiency delays long bone fracture healing by impairing endochondral ossification. HYBID-mediated HA depolymerization is crucial for effective bone repair.
Area of Science:
- Biochemistry
- Orthopedics
- Regenerative Medicine
Background:
- Hyaluronan (HA)-binding protein (HYBID) plays a role in HA degradation and influences ossification.
- HYBID promotes endochondral ossification but inhibits intramembranous ossification.
- The role of HYBID in long bone fracture healing, involving both ossification types, is largely unknown.
Purpose of the Study:
- To investigate the role of HYBID in murine long bone fracture healing.
- To determine the effects of genetic HYBID depletion on fracture repair processes.
Main Methods:
- Femoral diaphyseal fracture model in wild-type and Hybid-deficient mice.
- Micro-computed tomography (micro-CT) for fracture gap bridging assessment.
- Histological analysis of callus formation, vascularization, and cell activity (osteoclasts/chondroclasts).
- Analysis of gene expression (Il-6, TGF-β1, BMP2) and HA molecular weight in callus tissue.
Main Results:
- Hybid-deficient mice exhibited delayed fracture gap bridging and fusion.
- Resorption of cartilaginous callus was retarded in Hybid-deficient mice, with reduced osteoclasts/chondroclasts and vascularization.
- High-molecular-weight HA accumulated in Hybid-deficient callus, while low-molecular-weight HA promoted healing in both groups.
- HYBID expression was observed in osteoblasts and hypertrophic chondrocytes during fracture healing.
Conclusions:
- HYBID deficiency impairs endochondral ossification, leading to delayed bone fracture healing.
- HYBID-mediated depolymerization of high-molecular-weight HA is essential for efficient bone fracture repair.
- Modulating HA molecular weight, potentially via HYBID activity, could be a therapeutic strategy for fracture healing.
