Mark C Horowitz1, Joseph A Lorenzo. 1. Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut 06520-8071, USA. mark.horowitz@yale.edu
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: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. SUMMARY: 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.
Authors: David G T Hesslein; Jackie A Fretz; Yougen Xi; Tracy Nelson; Shoaming Zhou; Joseph A Lorenzo; David G Schatz; Mark C Horowitz Journal: Bone Date: 2008-12-16 Impact factor: 4.398