title: Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone.
abstract: Giant cell tumor (GCT) of bone is a unique bone lesion that is characterized by an excessive number of multinucleated osteoclasts. GCT consists of neoplastic stromal cells, multinucleated osteoclasts and their precursors, thus serving as a naturally occurring human disease model for the study of osteoclastogenesis. It still remains unclear how stromal cells of GCT recruit osteoclast precursors. In the present study, we characterized the cellular components of GCT and confirmed the presence of CD14(+)-monocytes/CD68(+)-macrophages and CD34(+)-hematopoetic stem cells that express CXCR4, a specific receptor for SDF-1; SDF-1 gene expression and presence of SDF-1 protein were confirmed by real time RT-PCR, in situ hybridization, and immunohistochemistry in the GCT tissue and cultured cells. SDF-1 was present at 25-50 ng/ml in the conditioned media from the GCT cultures, which is in the range of physiological chemotactic concentration. Migration of osteoclast precursors was 2.5-fold higher in response to GCT conditioned media compared to the control media; and migration was inhibited by an average of 36% with anti-SDF-1 neutralizing antibody or competing recombinant SDF-1. These results suggest that SDF-1 is one of the significant chemoattractant factors involved in the recruitment of hematopoietic osteoclast precursor cells during tumor-induced osteoclastogenesis.
authors.affiliation: Center for Orthopaedic Research, Department of Orthopaedic Surgery, Columbia University, 622 W. 168th Street, BHN816, New York, NY 10032, USA.
authors.forename: Ted S
authors.initials: TS
authors.lastname: Liao
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Yurgelun
authors.forename: Seong-Sil
authors.initials: SS
authors.lastname: Chang
authors.forename: Hui-Zhu
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Koko
authors.initials: K
authors.lastname: Murakami
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Blaine
authors.forename: May V
authors.initials: MV
authors.lastname: Parisien
authors.forename: William
authors.initials: W
authors.lastname: Kim
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Winchester
authors.forename: Francis Young-In
authors.initials: FY
authors.lastname: Lee
mesh_terms: D001859:Bone Neoplasms / Q000473:pathology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D018212:Giant Cell Tumor of Bone / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D009000:Monocytes / Q000276:immunology; D010010:Osteoclasts / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology*
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC