title: Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cell-derived factor-1 pathway.
abstract: 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.
authors.affiliation: Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Otsuru
authors.forename: Katsuto
authors.initials: K
authors.lastname: Tamai
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001775:Blood Circulation; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta