The origins of osteoclasts.
OBJECTIVE
It is now dogma that osteoclasts (OCs) arise from cells of the monocyte/macrophage lineage. However, data are accumulating suggesting that a relationship exists between B lymphocytes (B cells) and OC differentiation. Although the exact nature of this relation is unknown, it takes at least two forms. First, molecules that regulate B-cell growth and development have striking effects on OC lineage cells particularly at early stages of differentiation. Second, the possibility exists that pro-B cells can give rise to osteoclast-like cells (OCLs) in vitro and in vivo. Recent data indicate, at the least, that a regulatory relation exists between B lymphopoiesis and osteoclastogenesis.


RESULTS
Pax5 is a member of the multigene family that encodes the paired box transcription factors. Pax5 is expressed exclusively in B-lymphocyte lineage cells extending from early B220 pro-B cells to mature B cells. Mice made deficient in Pax5 have a developmental arrest of the B-cell lineage at the pro-B-cell stage. Pax5-/- pro-B cells could be induced to form OCLs by treatment with macrophage colony-stimulating factor and receptor activator of nuclear factor-kappaB ligand (RANKL). Importantly, Pax5-/- mice are severely osteopenic, missing more than 60% of their bone mass. This is the result of a three- to fivefold increase in the number of OCs in bone, whereas the number of osteoblasts is indistinguishable from controls.


CONCLUSIONS
The analysis of a variety of mutations in mice supports the hypothesis that B cells and OCs develop in parallel; that their development is regulated in a reciprocal manner; and that in the Pax5-deficient state, OCs arise from pro-B cells.
Horowitz
Mark C
MC
Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut 06520-8071, USA. mark.horowitz@yale.edu
Lorenzo
Joseph A
JA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006133:Growth Substances / Q000276:immunology; D006801:Humans; D051379:Mice; D010010:Osteoclasts / Q000276:immunology*; D015398:Signal Transduction
D016207:Cytokines; D006133:Growth Substances