EXPRESSION OF COLONY-STIMULATING FACTOR-I 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 differe ntiation of the cells of the osteoclast lineage, The cytokine is synth esized either as a secreted or a membrane-bound protein, which are enc oded by four transcripts. The aim of the present study was to investig ate the expression of CSF-1 in vivo at the mRNA level. Transcripts enc oding 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 tran scripts encoding CSF-1 could be detected in metatarsals from 15-day-ol d fetuses, Transcript levels increased slowly during the following day s to reach a maximum in the rudiments from 18-day-old fetuses, After b irth, in newborn animals, transcript levels were lowered again. While in rudiments fi om 15-day-old fetuses a considerable portion of the tr anscripts encoded the membrane-bound molecule, a transcript encoding t he secreted form of the cytokine was the predominant species during th e following days, These results suggest that the maintenance of prolif erating and postmitotic osteoclast precursors requires low levels of C SF-1 only. Highest levels of locally synthesized CSF-1 are required, h owever, during the initial recruitment and activation of osteoclasts, After birth, levels of CSF-1 transcripts decrease again, suggesting th at newly synthesized CSF-1 may be replaced by protein released from th e mineralized matrix during resorption, In conclusion, the present dat a further strengthen the notion that CSF-1 produced locally acts in a paracrine fashion during the formation of osteoclasts.