Circulating Bone Marrow‐Derived Osteoblast Progenitor Cells Are Recruited to the Bone‐Forming Site by the CXCR4/Stromal Cell‐Derived Factor‐1 Pathway

• Published in: Stem cells (Dayton, Ohio) Vol. 26; no. 1; pp. 223 - 234
• Main Authors: Otsuru, Satoru, Tamai, Katsuto, Yamazaki, Takehiko, Yoshikawa, Hideki, Kaneda, Yasufumi
• Format: Journal Article
• Language: English
• Published: Bristol John Wiley & Sons, Ltd 01.01.2008
• Subjects: Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Animals; Blood Circulation; Bone and Bones - cytology; Bone marrow cells; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - metabolism; Cell Movement - physiology; Chemokine CXCL12 - metabolism; Chemokine receptor CXCR4; Female; Flow Cytometry; Humans; Immunohistochemistry; Male; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mobilization kinetics; Osteoblast; Osteoblasts - cytology; Osteoblasts - metabolism; Osteogenesis - physiology; Peripheral blood Stromal derived factor‐1; Receptors, CXCR4 - metabolism; Recombinant Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Stem/progenitor cell; Tissue regeneration; Transforming Growth Factor beta - metabolism
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1634/stemcells.2007-0515

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. Disclosure of potential conflicts of interest is found at the end of this article.