Collagen-binding peptide reverses bone loss in a mouse model of cerebral palsy based on clinical databases

Yoon Kyum Shin, Jeong Hyun Heo, Jue Yeon Lee, Yoon Jeong Park, Sung Rae Cho

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalAnnals of Physical and Rehabilitation Medicine
DOIs
Publication statusAccepted/In press - 2020

Bibliographical note

Funding Information:
The study was supported by the National Research Foundation (NRF-2017R1D1A1B03028855; 2020R1I1A1A01071167) funded by the Ministry of Education, Republic of Korea . The CBP was provided by Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul National University, Republic of Korea. The authors thank Medical Illustration & Design, a part of the Medical Research Support Services of Yonsei University College of Medicine, for helping with illustrations related to the graphical abstract.

Funding Information:
The study was supported by the National Research Foundation (NRF-2017R1D1A1B03028855; 2020R1I1A1A01071167) funded by the Ministry of Education, Republic of Korea. The CBP was provided by Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul National University, Republic of Korea. The authors thank Medical Illustration & Design, a part of the Medical Research Support Services of Yonsei University College of Medicine, for helping with illustrations related to the graphical abstract.

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Rehabilitation

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