Localization of Bmi1 in osteoblast-lineage cells during endochondral ossification.

Encoded by B cell-specific moloney murine leukemia virus integration site 1, Bmi1 is part of the polycomb group of proteins localized in stem and undifferentiated cells. It regulates the expression of various differentiation genes. However, the regulatory mechanism of skeletal development by Bmi1 remains poorly understood. In this study, we aimed to observe Bmi1 distribution during endochondral ossification processes in rat bone development and fracture healing. Immunoreactivity of Bmi1 was detected in the mesenchymal cell aggregation area at embryonic day (E) 14 and in cells around the center of cartilage primordium at E 16. Subsequently, the calcified bone matrix was formed around the cartilage primordium, and osteoblasts expressing Runt-related transcription factor 2 (Runx2) and Osterix (Osx) showed immunopositivity for Bmi1. At 4 days after bone fracture, the connective tissue around the fractured bone contained Bmi1-positive cells. At 42 days after fracture, osteoblasts along the surface of the new bone revealed Bmi1-, Runx2- and Osx-positive reactions, but the Bmi1 immunoreactivity in osteocytes was less than the Runx2 and Osx immunoreactivities. In conclusion, Bmi1 is localized in the osteoblast-lineage cells in their early differentiation stages, and it might regulate their differentiation during endochondral ossification.