Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cell-derived factor-1 pathway
Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cell-derived factor-1 pathway
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DOI：
10.1634/stemcells.2007-0515
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Kaneda, Yasufumi
中科院分区：
文献类型：
--
作者：
Otsuru, Satoru;Tamai, Katsuto;Kaneda, Yasufumi
以往的研究表明，循环血液中存在成骨细胞。最近，我们报道了循环中的成骨细胞前体细胞(OPC)来源于骨髓，并参与了含有骨形态发生蛋白(BMP)-2的胶原粒植入小鼠肌肉组织中诱导异位骨的形成。然而，循环中的骨髓来源成骨细胞前体细胞(MOPC)的特性及其在成骨过程中的确切机制，如将循环中的MOPC募集到骨组织中的信号，目前还不清楚。在这篇报道中，我们首次证明了通过植入BMP-2微球，MOPC从完整的骨骼中被动员起来，瞬时占据了循环血液中约80%的单核细胞。动员后的MOPC表面不表达CD45，但分别表达骨桥蛋白受体CD44和基质细胞衍生因子-1(SDF-1)受体CXCR4。从小鼠外周血中分离出的MOPC在体外和体内均具有成骨细胞的能力。此外，循环中的MOPC通过在血管内皮细胞和成骨细胞中表达的SDF-1的化学吸引而有效地迁移到成骨区域。这些数据可能为了解循环血液中MOPC参与的骨形成机制提供新的见解，并为未来利用循环MOPC加速骨再生提供新的前景。
Previous studies demonstrated the existence of osteoblastic cells in circulating blood. Recently, we reported that osteoblast progenitor cells (OPCs) in circulation originated from bone marrow and contributed to the formation of ectopic bone induced by implantation of a bone morphogenetic protein (BMP)-2-containing collagen pellet in mouse muscular tissue. However, the character of circulating bone marrow-derived osteoblast progenitor cells (MOPCs) and the precise mechanisms involving the circulating MOPCs in the osteogenic processes, such as signals that recruit the circulating MOPCs to the osseous tissues, have been obscure. In this report, we demonstrated for the first time that the MOPCs were mobilized from intact bones to transiently occupy approximately 80% of the mononuclear cell population in the circulating blood by BMP-2-pellet implantation. The mobilized MOPCs in the circulation did not express the hematopoietic marker CD45 on their surface, but they expressed CD44 and CXCR4, receptors of osteopontin and stromal cell-derived factor-1 (SDF-1), respectively. The MOPCs isolated from the mouse peripheral blood showed the ability to be osteoblasts in vitro and in vivo. Furthermore, the MOPCs in the circulation efficiently migrated to the region of bone formation by chemoattraction of SDF-1 expressed in vascular endothelial cells and the de novo osteoblasts of the region. These data may provide a novel insight into the mechanism of bone formation involving MOPCs in circulating blood, as well as perspective on the use of circulating MOPCs to accelerate bone regeneration in the future.