Generation of Bone-Resorbing Osteoclasts from B220+ Cells: Its Role in Accelerated Osteoclastogenesis due to Estrogen Deficiency

Abstract

Estrogen deficiency stimulates both osteoclastic bone resorption and pre-B lymphopoiesis, the interrelationships between which remain unknown. To investigate the involvement of an increase in the number of B220 ؉ cells in accelerated osteoclastogenesis after estrogen deficiency, we first examined whether ovariectomy (OVX) increased the frequency of clonogenic osteoclast precursors in bone marrow. The results were that after OVX, the frequency of clonogenic osteoclast precursors is increased in bone marrow, suggesting that accumulated osteoclast precursors contribute to accelerated osteoclastogenesis. Further, we found that cocultures of B220

Receptor Activator of Nuclear Factor κB Ligand (RANKL) Protein Expression by B Lymphocytes Contributes to Ovariectomy-induced Bone Loss

“…It is also possible that the increased number of B lymphocytes may act as an additional source of osteoclast progenitors. Multiple studies have shown that isolated B lymphocytes can act as osteoclast progenitors, at least in vitro (16,(42)(43)(44)(45), although this has been attributed by some to contamination of the lymphocyte preparation with macrophage-lineage cells (46). In vivo lineage-tracing studies will be required to address this issue directly.…”

B cells activated in the presence of Th1 cytokines inhibit osteoclastogenesis

“…BTh2 expressed pro-osteolytic factors including RANKL, TNF-α, and TNF-β but low levels of strong suppres (Manabe et al, 2001). When we stained B cells with succinimidyl ester of carboxyfluorescein diacetate (CFSE) and co-cultured with RAW264.7 cells, none of the differentiated osteoclasts had fluorescence (data not shown), excluding the possibility that B cell themselves differentiate into osteoclasts as suggested from the shared lineage in these two cells (Sato et al, 2001). Compared with BTh2, BIL-2 expressed high levels of IFN-γ as well as RANKL, TNF-α, and TNF-β (Figure 2A).…”

Increased bone resorption and osteopenia are a part of the lymphoproliferative phenotype of mice with systemic over-expression of interleukin-7 gene driven by MHC class II promoter

“…Immune phenotype of IL-7 TG mice includes up to four-fold increase in CD45R + BM cells [9], which may also have OCL differentiation potential in vitro [19,20]. …”