Localized insulin-like growth factor I delivery to enhance new bone formation
| Autor: | Oscar E. Illi, Regula Bettschart-Wolfisberger, Rebecca Schneider, Bruno Gander, Evangelos Zoidis, Hans P. Merkle, Paulo Hassa, Jörg A Auer, Vera Luginbuehl, Brigitte von Rechenberg, Lorenz Meinel, Michael O. Hottiger, Jürgen Zapf |
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| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Histology Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Gene Expression Nitric Oxide Synthase Type II Bone healing Biology Bone resorption Bone remodeling Insulin-like growth factor Drug Delivery Systems Osteogenesis Internal medicine medicine Animals Insulin-Like Growth Factor I Bone regeneration Cells Cultured Fracture Healing Osteoblasts Sheep Interleukin-6 Bone Injury Growth factor NF-kappa B Microspheres Recombinant Proteins Isoenzymes Endocrinology medicine.anatomical_structure Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Immunology Female Bone Diseases Nitric Oxide Synthase Cancellous bone Interleukin-1 |
| Zdroj: | Bone. 33:660-672 |
| ISSN: | 8756-3282 |
| Popis: | Insulin-like growth factor I (IGF I) exerts an important role during skeletal growth and bone formation. Therefore, its localized delivery appears attractive for the treatment of bone defects. To prolong IGF I delivery, we entrapped the protein into biodegradable poly(lactide-co-glycolide) microspheres (PLGA MS) and evaluated the potential of this delivery system for new bone formation in two defect models of ovine long bones, i.e., a 8-mm methaphyseal drill hole and a 10-mm segmental tibia defect. Administration of 100 μg of IGF I in PLGA MS resulted in new bone formation within 3 weeks in the drill hole and bridging of the segmental defect within 8 weeks. The observed increase of 12% newly formed bone in the drill hole defect after 3 weeks was substantial, compared to the measured morphometric bone-to-total area ratio of 31% bone in normal cancellous bone. Bone regeneration was further explored by measuring gene expression of typical markers for local mediators and growth factors by real-time polymerase chain reaction. Inflammation was reduced in presence of IGF I and this in vivo observation was corroborated in vitro by quantifying gene expression of inflammatory proteins and by assessing the activation of the NF-κB pathway, playing an important role in the regulation of inflammation. Administration of the IGF I delivery system downregulated inflammatory marker gene expression at the site of bone injury, induced new bone formation and reduced bone resorption, and resulted in bridging of 10-mm segmental tibial defects within 8 weeks. |
| Databáze: | OpenAIRE |
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