The birth of the osteoclast

Thirty-five years ago it had become clear that the osteoclast was not a bone cell but an immigrant into bone, derived from the hemopoietic system. Among hemopoietic cells, mononuclear phagocytes seemed the most likely precursors. However, for the progeny of wandering cells such as those to achieve nonrandom localization implies control by the local bone cells (cells of the osteoblastic lineage). To test this idea, we extracted osteoclasts from bone and observed their behavior in culture. We noted that calcitonin induced a striking shape change, which reflected suppression of cytoplasmic motility. Because bone resorption is likely to depend on motile processes, we used this response to infer the regulation of osteoclasts by systemic and local hormones and osteoblastic cells. We went on to provide direct evidence for the predominantly osteoblastic regulation of osteoclasts by measuring the ability of isolated osteoclasts to resorb the surface of bone slices.