Collagen-binding peptide reverses bone loss in a mouse model of cerebral palsy based on clinical databases
Yoon-Kyum Shin1, Jeong Hyun Heo2, Jue Yeon Lee3
1Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, 03722 Seoul, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 03722 Seoul, Republic of Korea.
Background:
Individuals with cerebral palsy (CP) experience bone loss due to impaired weight bearing. Despite serious complications, there is no standard medication.
Objective:
To develop a new pharmacological agent, we performed a series of studies. The primary aim was to develop an animal model of CP to use our target medication based on transcriptome analysis of individuals with CP. The secondary aim was to show the therapeutic capability of collagen-binding peptide (CBP) in reversing bone loss in the CP mouse model.
Methods:
A total of 119 people with CP and 13 healthy adults participated in the study and 140 mice were used for the behavioral analysis and discovery of therapeutic effects in the preclinical study. The mouse model of CP was induced by hypoxic-ischemic brain injury. Inclusion and exclusion criteria were established for CBP medication in the CP mouse model with bone loss.
Results:
On the basis of clinical outcomes showing insufficient mechanical loading from non-ambulatory function and that underweight mainly affects bone loss in adults with CP, we developed a mouse model of CP with bone loss. Injury severity and body weight mainly affected bone loss in the CP mouse model. Transcriptome analysis showed SPP1 expression downregulated in adults with CP who showed lower bone density than healthy controls. Therefore, a synthesized CBP was administered to the mouse model. Trabecular thickness, total collagen and bone turnover activity increased with CBP treatment as compared with the saline control. Immunohistochemistry showed increased immunoreactivity of runt-related transcription factor 2 and osteocalcin, so the CBP participated in osteoblast differentiation.
Conclusions:
This study can provide a scientific basis for a promising translational approach for developing new anabolic CBP medication to treat bone loss in individuals with CP.
Insights
A new collagen-binding peptide (CBP) shows promise in treating bone loss in individuals with cerebral palsy (CP). This study developed a CP mouse model and demonstrated CBP
Area of Science:
- Orthopedics
- Pharmacology
- Genetics
Background:
- Cerebral palsy (CP) is associated with significant bone loss due to impaired weight-bearing.
- Current treatments for bone loss in CP are lacking, necessitating novel therapeutic strategies.
Purpose of the Study:
- To develop a CP mouse model for evaluating therapeutic agents.
- To investigate the potential of collagen-binding peptide (CBP) in reversing bone loss in CP.
Main Methods:
- Developed a CP mouse model using hypoxic-ischemic brain injury.
- Conducted transcriptome analysis on CP patient samples to identify therapeutic targets.
- Administered synthesized CBP to the CP mouse model and assessed bone parameters.
Main Results:
- Transcriptome analysis revealed downregulated SPP1 expression in CP patients with lower bone density.
- CBP treatment in the CP mouse model significantly increased trabecular thickness, total collagen, and bone turnover.
- Evidence suggests CBP promotes osteoblast differentiation, indicated by increased runt-related transcription factor 2 and osteocalcin.
Conclusions:
- The developed CP mouse model is suitable for preclinical drug evaluation.
- Collagen-binding peptide (CBP) demonstrates therapeutic potential for treating bone loss in cerebral palsy.
- This research provides a foundation for developing anabolic CBP medications for CP-related bone loss.
