title: Osteoblast lineage properties in giant cell tumors of bone.
abstract: BACKGROUND
  Giant cell tumors of bone (GCTs), among the most common primary bone tumors, are characterized by the formation of abundant osteoclast-like multinucleated giant cells (MNCs). It is not yet clear about the origin of GCTs and which cells in the lesion are the true neoplastic component. Several recent reports suggested that MNCs are osteoclasts induced by stroma-like tumor cells expressing the ligand for receptor activator of NF-kappaB (RANKL), which is a membrane-bound osteoclast differentiation factor. This hypothesis suggests an osteoblast lineage origin of GCTs, although it has long been speculated about GCTs being of mesenchymal stem cell (MSC) origin.
  
  
  METHODS
  We investigated the expression of osteoblastic differentiation markers in 10 human GCTs by reverse transcription-polymerase chain reaction and immunohistochemistry. We also performed osteoblastic and adipogenic differentiation assays using cultured cells derived from surgically resected lesions to estimate the stem cell-like properties.
  
  
  RESULTS
  GCTs and derived stromal cells expressed many osteoblast lineage marker genes, such as collagen type I, bone sialoprotein, core binding factor a-1, and osteocalcin. Instead of stable expression of mRNA, osteocalcin was not detected among the proteins. The tumor-derived cultures showed osteoblastic but not adipogenic differentiation capability. These findings strongly suggest that GCTs are of osteoblast lineage origin.
  
  
  CONCLUSIONS
  Our results indicated that GCTs expressed many osteoblastic markers and showed properties of pre-osteoblast-like cells rather than those of MSCs. These observations may provide some insight into the mechanisms of disease progression and the origin of GCTs.
authors.affiliation: Department of Orthopaedic Surgery, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Murata
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujita
authors.forename: Norio
authors.initials: N
authors.lastname: Kawahara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tomita
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D015675:Osteocalcin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015675:Osteocalcin