DETECTION OF TRANSCRIPTS AND BINDING-SITES FOR COLONY-STIMULATING FACTOR-I DURING BONE-DEVELOPMENT

Colony-stimulating factor-1 (CSF-1), originally characterized as the g rowth factor for the cells of the mononuclear phagocytic system, has b een shown to be essential for osteoclast formation. The aim of the pre sent study was twofold: (i) to investigate the expression of transcrip ts encoding CSF-1; and (ii) to detect binding sites for CSF-1 during b one development. As a model, metatarsal rudiments from embryonic mice of different ages were used, an in vivo system allowing one to follow osteoclast formation. In 16-day-old embryos, proliferating osteoclast precursors are located on the outer surface of the rudiments. They dif ferentiate subsequently to post-mitotic precursors. At 18 days, the pr ecursors fuse and the mature osteoclasts invade the mineralized cartil age of the rudiments to excavate the future bone marrow cavity. Within this study, in situ hybridization on sections of whole paws from 17-d ay-old embryos revealed CSF-1 transcripts to be present in cells linin g the outside of the midregion of the metatarsals. One day later, cell s containing CSF-1 mRNA were found within the mineralized cartilage. T he levels of transcripts encoding CSF-1 were further increased in the bone rudiments of newborn animals. Binding sites for CSF-1 on cells in close proximity of the metatarsals were detected at embryonic age 17 days, but not before. At this stage, cells binding CSF-1 were located on the periosteum of the midregion of the metatarsal rudiment. At 18 d ays, cells expressing high levels of CSF-1 binding sites had invaded t he mineralized cartilage. Furthermore, the growth factor was shown to be bound by isolated osteoclasts. These binding studies demonstrated t hat CSF-1 binding sites are present on osteoclast precursors and on th e mature osteoclasts. In conclusion, the presented results suggest tha t CSF-1 might act directly on the cells of the osteoclastic lineage an d that it is locally synthesized during the terminal differentiation s teps of these cells.