PTH Signaling in Osteoprogenitors Is Essential for B-Lymphocyte Differentiation and Mobilization
PTH Signaling in Osteoprogenitors Is Essential for B-Lymphocyte Differentiation and Mobilization
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DOI：
10.1002/jbmr.2581
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发表时间：
2015-12-01
影响因子：
6.2
通讯作者：
Wu, Joy Y.
中科院分区：
文献类型：
--
作者：
Panaroni, Cristina;Fulzele, Keertik;Wu, Joy Y.
成骨细胞系的细胞为骨髓中B淋巴细胞的生成提供关键支持。甲状旁腺激素(PTH)通过其受体(PPR)在成骨细胞中的信号转导是造血干细胞的重要调节因子，但其在B淋巴细胞生成调控中的作用尚不清楚。在这里，我们证明了在骨祖细胞中PPR的缺失会导致骨小梁和皮质骨的显著丢失。在成骨细胞或成骨细胞中，PPR信号对B细胞前体产生IL-7的分化至关重要。有趣的是，尽管骨髓中的B细胞前体细胞严重减少，但在骨祖细胞中缺乏PPR的小鼠的骨髓中成熟的B淋巴细胞增加了3.5倍。这种成熟的IGD(+)B细胞在骨髓中的保留与PPR缺陷的骨祖细胞表达血管细胞黏附分子1(VCAM1)有关，而VCAM1中和抗体治疗增加了突变BM中B淋巴细胞的动员。我们的结果表明，早期成骨细胞中的PPR信号对B细胞通过分泌IL-7分化和通过VCAM1动员B细胞是必要的。(C)2015年美国骨与矿物研究学会。
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. (C) 2015 American Society for Bone and Mineral Research.