Connection Between B Lymphocyte and Osteoclast Differentiation Pathways

• Published in: The Journal of immunology (1950) 2001-09, Vol.167 (5), p.2625-2631
• Main Authors: Manabe, Noriyo, Kawaguchi, Hiroshi, Chikuda, Hirotaka, Miyaura, Chisato, Inada, Masaki, Nagai, Ryozo, Nabeshima, Yo-ichi, Nakamura, Kozo, Sinclair, Angus M, Scheuermann, Richard H, Kuro-o, Makoto
• Format: Article
• Language: English
• Subjects: Aging - genetics; Aging - pathology; Animals; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Base Sequence; Carrier Proteins - physiology; Cell Differentiation - genetics; Cell Differentiation - physiology; DNA Primers - genetics; Glucuronidase; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; Membrane Glycoproteins - physiology; Membrane Proteins - genetics; Membrane Proteins - physiology; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; ODF/RANKL protein; osteoclast differentiation factor; Osteoclasts - cytology; Osteoclasts - physiology; Osteoporosis - etiology; Osteoporosis - genetics; Osteoporosis - pathology; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; TRANCE protein
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.5.2625

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.