Induction of periosteal bone formation by intraosseous BMP-2 injection in a mouse model of osteogenesis imperfecta
| Autor: | David G. Little, Tegan L. Cheng, Laurence C. Cantrill, Aaron Schindeler |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
030222 orthopedics
0303 health sciences business.industry Dentistry osteogenesis imperfecta medicine.disease Bone morphogenetic protein 2 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Basic Science Osteogenesis imperfecta BMP-2 Pediatrics Perinatology and Child Health medicine Orthopedics and Sports Medicine business Sucrose acetate isobutyrate Periosteal bone formation Surgical interventions sucrose acetate isobutyrate 030304 developmental biology |
| Zdroj: | Journal of Children's Orthopaedics |
| ISSN: | 1863-2521 |
| Popis: | Purpose Surgical interventions are routinely performed on children with osteogenesis imperfecta (OI) to stabilize long bones, often post fracture. We speculated that a combination of intramedullary reaming and intraosseous injection of recombinant bone morphogenetic protein-2 (BMP-2) could enhance periosteal ossification and ultimately cortical thickness and strength. This approach was conceptually tested in a preclinical model of genetic bone fragility. Methods Six experimental groups were tested including no treatment, intramedullary reaming, and reaming with 5 µg BMP-2 injection performed in the tibiae of both wild type (WT) and Col1a2 G610C/+ (OI, Amish mutation) mice. Bone formation was examined at a two-week time point in ex vivo specimens by micro-computed tomography (microCT) analysis and histomorphometry with a dynamic bone label. Results MicroCT data illustrated increases in tibial cortical thickness with intramedullary reaming alone (Saline) and reaming plus BMP-2 injection (BMP-2) compared to no intervention controls. In the OI mice, the periosteal bone increase was not statistically significant with Saline but there was an increase of +192% (p = 0.053) with BMP-2 injection. Dynamic histomorphometry on calcein label was used to quantify new woven bone formation; while BMP-2 induced greater bone formation than Saline, the anabolic response was blunted overall in the OI groups. Conclusions These data indicate that targeting the intramedullary compartment via reaming and intraosseous BMP-2 delivery can lead to gains in cortical bone parameters. It is suggested that the next step is to validate safety and functional improvements in a clinical OI setting. |
| Databáze: | OpenAIRE |
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