The Origin of Osteoclasts

There are two kinds of cells involved in bone remodeling: osteocblasts and osteoclasts. Unlike osteoblasts, which differentiated from uncommitted mesenchymal cells[1], evidences clearly show that osteoclasts are hematopoietic origin. They arise from hematopoietic stem cells reside in both bone marrow and spleen. Osteoclast differentiation undergoing three steps: the formation of monocytic precursors (M-CSF dependent), the formation of osteoclast progenitors (osteoclast defferentiation factors dependent), mononucleated tartrate-resistant acidic phosphatase (TRAP) positive pre-osteoclast precursors, and the formation of mature, multinucleated osteoclasts.

Bone or bone-like microenvironment is necessary for osteoclast differentiation. In vitro co-culture experiments showed that the contact between osteoclast progenitors and osteoblasts is indeed providing the microenvironment. The conditional medium from osteoblast cultures failed to induce osteoclast differentiation, suggesting that the stimuli from osteoblasts are cell membrane proteins. One of the key proteins was later on identified as RANKL (receptor activator of NF-Kb ligand).

1. Osdoby, P., et al., The origin, development and regulation of osteoclasts. Bioessays, 1987. 7(1): p. 30-4.