Connection between B lymphocyte and osteoclast differentiation pathways.
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-kappaB 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.
Manabe
N
N
Department of Orthopaedic Surgery and Cardiovascular Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Kawaguchi
H
H
Chikuda
H
H
Miyaura
C
C
Inada
M
M
Nagai
R
R
Nabeshima
Y
Y
Nakamura
K
K
Sinclair
A M
AM
Scheuermann
R H
RH
Kuro-o
M
M
D000375:Aging / Q000235:genetics / Q000473:pathology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005966:Glucuronidase; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D000090265:Klotho Proteins; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology; D010024:Osteoporosis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
D002352:Carrier Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D005966:Glucuronidase; D000090265:Klotho Proteins