| The osteoclast, the primary cell which resorbs bone, is known to have a hematopoietic origin; however, the precise relationship of osteoclasts to other hematopoietic cells and the differentiation pathway of osteoclasts are yet to be determined. In order to clarify the lineage divergence and differentiation of osteoclasts from hematopoietic stem cells, this investigation examines the cell surface phenotypes of osteoclasts and other hematopoietic progenitors and compares the behavior of these progenitors in various culture conditions. Although osteoclast progenitors express a cell surface molecule, c-kit, which is also expressed by other hematopoietic progenitors, their growth factor requirement for survival and differentiation are discrete from those of other hematopoietic progenitors. They survive longer in an exogenous growth factor free condition, and their differentiation is independent of interaction between c-kit and its ligand, stem cell factor (SCF). This is the first comparative study of osteoclast and other hematopoietic progenitors, which successfully demonstrates exceptional behavior of osteoclast progenitors.;Using a sequential cell fractionation technique, this study has identified a murine bone marrow cell population which is selectively enriched for osteoclast progenitors. This population, which represents only 0.01% of whole bone marrow cells, is characterized by its non-adherent, low density, lineage marker negative, Thy1.2 negative, and Sca1 negative properties, and also the low expression of c-kit. Eighty % of the progenitors present in this population are osteoclast progenitors, and all colonies developed from the isolated osteoclast progenitor population differentiated into osteoclasts in a colony-stromal cell co-culture system. Also, the sequential expression of osteoclast markers during the differentiation of osteoclasts from immature progenitor cells has been revealed using immunohistochemistory and autoradiography techniques.;This work suggests that osteoclasts develop from unique progenitor cells. The progenitor cells are marked by their distinct cell surface phenotypes, longer survival in an exogenous growth factor free condition, and c-kit-SCF independent differentiation. |
