Connection between B lymphocyte and osteoclast differentiation pathways

N. Manabe, H. Kawaguchi, H. Chikuda, C. Miyaura, M. Inada, R. Nagai, Y. I. Nabeshima, K. Nakamura, A. M. Sinclair, R. H. Scheuermann, M. Kuro-o

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

Abstract

Osteoclasts differentiate from the hemopoietic monocyte/macrophage cell lineage in bone marrow through cell-cell interactions between osteoclast progenitors and stromal/osteoblastic cells. Here we show another osteoclast differentiation pathway closely connected with B lymphocyte differentiation. Recently the TNF family molecule osteoclast differentiation factor/receptor activator of NF-κB ligand (ODF/RANKL) was identified as a key membrane-associated factor regulating osteoclast differentiation. We demonstrate that B-lymphoid lineage cells are a major source of endogenous ODF/RANKL in bone marrow and support osteoclast differentiation in vitro. In addition, B-lymphoid lineage cells in earlier developmental stages may hold a potential to differentiate into osteoclasts when stimulated with M-CSF and soluble ODF/RANKL in vitro. B-lymphoid lineage cells may participate in osteoclastogenesis in two ways: they 1) express ODF/RANKL to support osteoclast differentiation, and 2) serve themselves as osteoclast progenitors. Consistent with these observations in vitro, a decrease in osteoclasts is associated with a decrease in B-lymphoid cells in klotho mutant mice (KL-/-), a mouse model for human aging that exhibits reduced turnover during bone metabolism, rather than a decrease in the differentiation potential of osteoclast progenitors. Taken together, B-lymphoid lineage cells may affect the pathophysiology of bone disorders through regulating osteoclastogenesis.

Original languageEnglish (US)
Pages (from-to)2625-2631
Number of pages7
JournalJournal of Immunology
Volume167
Issue number5
DOIs
StatePublished - Sep 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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