Expression of colony-stimulating factor-1 in vivo during the formation of osteoclasts

Colony-stimulating factor-1 (CSF-1), originally described as a growth factor for macrophages, is essential for the proliferation and differentiation of the cells of the osteoclast lineage. The cytokine is synthesized either as a secreted or a membrane-bound protein, which are encoded by four transcripts. The aim of the present study was to investigate the expression of CSF-1 in vivo at the mRNA level. Transcripts encoding CSF-1 were determined in total RNA from fetal murine metatarsals of different ages by a quantitative reverse-transcription polymerase chain reaction assay. Within the investigated period of time, the bone rudiments contain cells of the osteoclastic lineage representing well-defined differentiation stages. We found that only low levels of transcripts encoding CSF-1 could be detected in metatarsals from 15-day-old fetuses. Transcript levels increased slowly during the following days to reach a maximum in the rudiments from 18-day-old fetuses. After birth, in newborn animals, transcript levels were lowered again. While in rudiments from 15-day-old fetuses a considerable portion of the transcripts encoded the membrane-bound molecule, a transcript encoding the secreted form of the cytokine was the predominant species during the following days. These results suggest that the maintenance of proliferating and postmitotic osteoclast precursors requires low levels of CSF-1 only. Highest levels of locally synthesized CSF-1 are required, however, during the initial recruitment and activation of osteoclasts. After birth, levels of CSF-1 transcripts decrease again, suggesting that newly synthesized CSF-1 may be replaced by protein released from the mineralized matrix during resorption. In conclusion, the present data further strengthen the notion that CSF-1 produced locally acts in a paracrine fashion during the formation of osteoclasts.