Immunohistochemical and in-situ hybridization study of hypoxia inducible factor-1α and angiopoietin-1 in a rabbit model of mandibular distraction osteogenesis

The endogenous release of angiogenic factors in a rabbit mandibular distraction osteogenesis model was investigated. The spatial and temporal expression of hypoxia inducible factor-1α (HIF-1α) and angiopoietin-1 (Ang-1) was compared at different phases. The lengthened calluses were harvested on post-osteotomy days 13, 20, 34 and 48, and then stained with haematoxylin & eosin. Immunohistochemical (IHC) and in-situ hybridization (ISH) examination of HIF-1α and Ang-1 staining was performed. The ossification in the distracted gap was predominantly intramembranous and slightly endochondral. Expression of HIF-1α and Ang-1 was mainly detected in the cytoplasm of fibroblast-like cells, osteoblasts and immature osteocytes on day 13 and 20, but declined with bone maturation. HIF-1α was also detected in the nuclei of some osteoblasts. These results suggest that the production of HIF-1α and Ang-1 in the distracted gap may contribute to new bone formation during gradual distraction of the mandible.