The origin and fate of osteoclasts

Despite intensive and ingenious investigation, the origins and ultimate fate of the osteoclast remain shrouded in mystery. This brief review evaluates some of the recent experimental approaches used in the study of the osteoclast, especially whether they form from intra- or extra-skeletal progenitor cells, whether from the same osteoprogenitor cell as the osteoblast, and whether, once formed, they may modulate to osteoblasts. That osteoprogenitor cells can, and do, become osteoclasts is well founded, as is the conclusion that such progenitor cells originate as blood-borne, extra-skeletal cells. Evidence that sessile, intra-skeletal, progenitor cells can form osteoclasts is less direct. There is good evidence that osteoclasts both shed and take-up nuclei, but no direct evidence that nuclear shedding is accompanied by death of the osteoclast, and no direct evidence for the fate of the shed nuclei. Whether the same osteoprogenitor cell can produce either an osteoblast or an osteoclast also remains an open question.