Lineage-committed osteoclast precursors circulate in blood and settle down into bone

Osteoclasts are derived from the monocyte/macrophage lineage, but little is known about osteoclast precursors in circulation. Bone marrow cells were subdivided into three populations; RANKhighFmslow, RANKhighFmshigh and RANKlowFmshigh. GeneChip analysis confirmed that the expression levels of monocyte-macrophage markers such as Emr1 (F4/80), Itgam (CD11b) and Csf1 (c-Fms) were lower in the RANKhighFmslow than RANKlowFmshigh population. In contrast, cells in the RANKhighFmslow population expressed higher levels of osteoclast markers such as Car ll (carbonic anhydrase ll), Mmp9 (matrix metalloproteinase 9), Acp5 (acid phosphatase 5) and Tfrc (transferrin receptor). These results suggest that RANKhighFmslow cells express few of the phenotypes of monocytes, and their differentiation into osteoclasts occurs at a slightly more advanced stage than that of the RANKlowFmshigh population. RANKhighFmslow cells and RANKlowFmshigh cells were isolated from bone marrow in ddY mice by FACS (Fluorescent activated cell sorting). Differential expression levels of mRNA were determined by GeneChip analysis.