Yoon Kyum Shin
Yonsei University College of Medicine, Republic of Korea
Title: Therapeutic effects of the collagen-binding motif as a novel osteoporosis medication in cerebral palsy with bone loss
Biography
Biography: Yoon Kyum Shin
Abstract
Cerebral palsy (CP) is a static lesion occurring in the immature brain from multifactorial causes including hypoxicischemia, resulting a life long motor impairment. Of note, severe patients with CP suffer from bone loss due to prolonged conditions of limited weight bearing in adulthood. In the transcriptome analysis, osteopontin (SPP1) gene expression in the peripheral blood mononuclear cells was significantly down regulated in adults with CP (n=13) than healthy adults. (n=13; fold change=-70.10). The osteopontin has multifaceted function of biomineralization by involving bone resorption and formation. A novel collagen binding motif (CBM) of osteopontin, is recently identified to induce bone formation via facilitating osteogenesis and inhibiting adipogenesis. We aim to propose reasonable therapeutic evidences for patients with CP who have osteopenia or osteoporosis by applying a novel osteoporosis medication in an animal model of neonatal hypoxic-ischemic (HI) brain injury. 7-day-old CD-1 pup mice underwent ischemic brain injury induced by unilateral right common carotid artery ligation and induced hypoxic condition. Severe HI brain injured mice were included to CBM administration for eight weeks. In the bone geometrical analysis, bone surface density and trabecular number were significantly increased after long term administration of CBM, while trabecular separation was significantly reduced compared to saline control. Through enzyme linked immunosorbent assay, we identified bone turnover markers including C - terminal telopeptide and procollagen type I were highly regulated in CBM treatment group compared to saline control. In an animal model of neonatal hypoxic-ischemic (HI) brain injury, the CBM improved bone geometrical components and bone turn over activity. This clinically translational investigation using the CBM shed lights on therapeutic administration for bone loss in adults with CP.