Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclast formation of human blood monocytes without cell to cell contact

• Published in: Journal of orthopaedic research 2005-09, Vol.23 (5), p.979-987
• Main Authors: Nishimura, Makoto, Yuasa, Kimitaka, Mori, Kouki, Miyamoto, Noriki, Ito, Morihiro, Tsurudome, Masato, Nishio, Machiko, Kawano, Mitsuo, Komada, Hiroshi, Uchida, Atsumasa, Ito, Yasuhiko
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - analysis; Bone Neoplasms - pathology; Carrier Proteins - genetics; Carrier Proteins - physiology; Cbfa1; Cell Communication; Cell Lineage; Cytokines - biosynthesis; Cytokines - genetics; Giant cell tumor derived stromal cells; Giant Cell Tumors - pathology; Humans; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Monocytes - cytology; Osteoblasts; Osteocalcin; Osteocalcin - analysis; Osteoclasts - physiology; Osteogenesis; Osteopontin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Calcium-Sensing - genetics; RNA, Messenger - analysis; Sialoglycoproteins - physiology; Soluble RANKL; Stromal Cells - cytology; Stromal Cells - physiology
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1016/j.orthres.2005.01.004

When human blood monocytes were cocultured with stromal cells derived from human giant cell tumor of bone (GCTSC) and a Millipore filter (0.4 μm) was interposed between monocytes and GCTSC, multinucleated giant cell formation of monocytes was induced. The multinucleated giant cells have characters as osteoclast-like cells, indicating that a soluble osteoclast-inducing factor(s) is secreted from GCTSC expressing RANK, RANKL/ODF/OPGL and TACE mRNA. Furthermore, OCIF/OPG inhibited GCTSC-induced osteoclastogenesis, showing that the RANK–RANKL system is involved in GCTSC-induced osteoclastogenesis and that soluble form of ODF/RANKL induces osteoclasts from monocytes. GCTSC expressed the cytokine mRNAs such as M-CSF, GM-CSF, IL-3, IL-4, IL-6, and IFN-γ mRNAs. None of IL-1rα, IL-1α, IL-1β, IL-2, IL-4, IL-10, IL-18, TNF-α, G-CSF and IFN-γ could be detected in all culture media. A significant amount of IL-6 could be detected in the culture media of all GCTSC. IL-8 was found in the culture media of two GCTSC and two osteosarcoma-derived cells. M-CSF was detected in all culture media. GCTSC express CaSR, and stimulation of GCTSC with either extracellular Ca 2+ or neomycin, agonist of CaSR, augumented the expression of RANKL. Some lines of GCTSC expressed alkaline phosphatase, osteocalcin and Cbfa1, suggesting that GCTSC are intimately related to osteoblastic lineage.