B-Lymphocytes are Elevated in Mouse Bone Marrow by Estrogen Deficiency, and Induce Receptor Activator of Nuclear Factor .KAPPA.B Ligand (RANKL) Expression in Osteoblasts via Cell Adhesion

Abstract

Loss of estrogen caused by ovariectomy (OVX) stimulates bone resorption and bone marrow B-lymphopoiesis, resulting in a marked bone loss and an accumulation of B cells in mouse bone marrow. In OVX mice, the expression of receptor activator of nuclear factor κB ligand (RANKL) mRNA was elevated in trabecular bone and bone marrow compared with sham mice. To examine the roles of B-lymphocytes in bone resorption, B cells were purified from bone marrow, fixed, and co-cultured with mouse osteoblasts. Most of the fixed B cells adhered to cell surface of osteoblasts. The expression of RANKL mRNA in osteoblasts was markedly elevated by the contact with the fixed B cells, and the induction rate of RANKL was correlated with the number of B cells added. Treatment with inhibitors of ERK 1/2 and p38 MAP kinases suppressed the B cell-induced RANKL expression in osteoblasts, suggesting the involvement of these kinases in the signals via the cell-to-cell contact. These findings emphasize the roles of B-lymphocytes in RANKL-induced osteoclastogenesis and in pathogenesis of bone loss due to estrogen deficiency.