Development of Osteoclasts From Embryonic Stem Cells Through a Pathway

Osteoclasts are hematopoietic cells essential for bone reclasts produced by 75% and more than 99%, respectively. sorption. To study the derivation of these interesting cells, Blockade of signaling through another tyrosine kinase–type we developed a stepwise culture system where stromal cells receptor, c-kit, did not affect any stages of osteoclastogenpromote embryonic stem (ES) cells to differentiate into maesis, although generation of other hemopoietic lineages was ture osteoclasts. Three phases to this differentiation process reduced to less than 10% of untreated. When small numbers include (1) induction of hematopoiesis, along with the generof ES cells were directly cultured under conditions that proation of osteoclast precursors, (2) expansion of these precurmote osteoclast differentiation, tartrate-resistant acid phossors, and (3) terminal differentiation into mature osteoclasts phatase-positive multinucleated cells were observed at the in the presence of 1a,25-dihydroxyvitamine D3. Although the edge but not inside of colonies. This suggests that some transition of ES cells to the hematopoietic lineage was not types of cell-cell interactions may inhibit development of blocked by an antibody to c-fms, later phases were depenmature osteoclasts. The culture system developed here prodent on a signaling through this transmembrane receptor vides an important tool for osteoclast biology. as indicated by the finding that anti–c-fms treatment of cells q 1997 by The American Society of Hematology. in the second and third phases reduced the number of osteo-