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PTH Signaling in Osteoprogenitors Is Essential for B‐Lymphocyte Differentiation and Mobilization
Author(s) -
Panaroni Cristina,
Fulzele Keertik,
Saini Vaibhav,
Chubb Rhian,
Pajevic Paola Divieti,
Wu Joy Y
Publication year - 2015
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.2581
Subject(s) - mobilization , lymphocyte , immunology , signal transduction , microbiology and biotechnology , biology , medicine , political science , law
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.