Circulating cells with osteogenic potential.

While osteoclast lineage cells are clearly present in the peripheral circulation, whether there is a comparable pool of circulating osteoblast lineage cells has remained controversial. Using assays requiring adherence to plastic (as originally described by Friedenstein and colleagues for bone marrow stromal cells over four decades ago), several studies have shown that plastic adherent cells with osteogenic potential are, indeed, present in the circulation of a number of species, but at extremely low concentrations. Work from a number of independent groups over the past decade has also identified a population of nonadherent bone marrow cells with osteogenic potential. Since these nonadherent cells may be much more likely to access the peripheral circulation than plastic adherent cells, we tested for the presence of circulating osteoblast lineage cells in humans using flow cytometry to identify cells in the peripheral blood expressing bone-related proteins. Our findings indicate that these cells are present in the circulation in significant numbers, are markedly increased in the peripheral blood of adolescent boys going through the growth spurt, and may also increase following fractures. These circulating osteogenic cells express bone-related proteins, can mineralize in vitro, and form bone in vivo. The identification of these osteogenic cells in peripheral blood opens up new questions regarding the possible role of these cells in bone remodeling, in fracture repair, and possibly in vascular calcification.