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PTH Signaling in Osteoprogenitors Is Essential for B-Lymphocyte Differentiation and Mobilization.
PTH Signaling in Osteoprogenitors Is Essential for B-Lymphocyte Differentiation and Mobilization. Journal of bone and mineral research Panaroni, C., Fulzele, K., Saini, V., Chubb, R., Pajevic, P. D., Wu, J. Y. 2015; 30 (12): 2273-2286Abstract
Cells of the osteoblast lineage provide critical support for B lymphopoiesis in the bone marrow (BM). Parathyroid hormone (PTH) signaling in osteoblastic cells through its receptor (PPR) is an important regulator of hematopoietic stem cells; however, its role in regulation of B lymphopoiesis is not clear. Here we demonstrate that deletion of PPR in osteoprogenitors results in a significant loss of trabecular and cortical bone. PPR signaling in osteoprogenitors, but not in mature osteoblasts or osteocytes, is critical for B-cell precursor differentiation via IL-7 production. Interestingly, despite a severe reduction in B-cell progenitors in BM, mature B-lymphocytes were increased 3.5-fold in the BM of mice lacking PPR in osteoprogenitors. This retention of mature IgD(+) B cells in the BM was associated with increased expression of vascular cell adhesion molecule 1 (VCAM1) by PPR-deficient osteoprogenitors, and treatment with VCAM1 neutralizing antibody increased mobilization of B lymphocytes from mutant BM. Our results demonstrate that PPR signaling in early osteoblasts is necessary for B-cell differentiation via IL-7 secretion and for B-lymphocyte mobilization via VCAM1. © 2015 American Society for Bone and Mineral Research.
View details for DOI 10.1002/jbmr.2581
View details for PubMedID 26191777