The origin of the osteoclast

The origin of the osteoclast remains controversial even though investigations using light microscopy, tissue culture, electron microscopy, microcinematography, autoradiography, parabiosis, quail chick nuclear markers, giant lysosomal markers in beige mice, Y chromosomes, bone marrow cell culture, and monoclonal antibodies have been performed since its discovery. Concepts of the origin of the osteoclast have been changing. The classic concept was that the osteoclast originated from connective tissue cells. Others hypothesized that it originated from mature hematopoietic cells, particularly from monocyte or macrophage cells. A recent concept proposed an origin from hematopoietic stem cells. The hematopoietic stem cell was believed to differentiate into two cell lineages: one of monocytes and the other of preosteoclasts. The authors' concept, based on experimental observations as well as alternate interpretations stemming from experimental reports of other researchers, proposes an origin from local, nonhematopoietic, possibly perivascular mesenchymal cells. However, the relationship of the hematopoietic stem cells to perivascular mesenchymal cells in the periosteum at an early stage of enchondral ossification is still not well known. Therefore, the origin of the osteoclast also remains uncertain.