title: Evidence for an autocrine/paracrine role for interleukin-6 in bone resorption by giant cells from giant cell tumors of bone.
abstract: Interleukin-6 (IL-6) is a multifunctional cytokine whose role in osteoclastic bone resorption has not been clearly defined. Therefore, we have used giant cells, which express many features of osteoclasts, from giant cell tumors of bone as a model to examine the role that IL-6 may play in human osteoclastic bone resorption. We found that conditioned medium from 24-h cultures of highly purified giant cells (10(6)/ml) contained large amounts of IL-6 (37.9 +/- 8.8 ng/ml), similar to the amount of IL-6 produced by tumor stromal cells (29.8 +/- 11.5 ng/ml). Giant cells and stromal cells from giant cell tumors expressed IL-6 mRNA, as indicated by polymerase chain reaction analysis and in situ hybridization studies, and immunohistochemical techniques demonstrated that the giant cells expressed IL-6 receptors. The addition of a neutralizing antibody to IL-6 significantly decreased the area of dentine resorbed by purified giant cells in a dose-dependent manner, and the addition of IL-6 to cultures of purified giant cells pretreated with anti-IL-6 restored the resorbing capacity of the giant cells. These data suggest that IL-6 may act as both an autocrine and a paracrine factor for human osteoclasts and play an important role in the bone-resorbing capacity of these cells.
authors.affiliation: Veterans Administration Medical Center, San Antonio, Texas.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohsaki
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Scarcez
authors.forename: A
authors.initials: A
authors.lastname: Demulder
authors.forename: T
authors.initials: T
authors.lastname: Nishihara
authors.forename: R
authors.initials: R
authors.lastname: Williams
authors.forename: G D
authors.initials: GD
authors.lastname: Roodman
mesh_terms: D001483:Base Sequence; D001859:Bone Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D001862:Bone Resorption; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005870:Giant Cell Tumors / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011971:Receptors, Immunologic / Q000032:analysis; D019947:Receptors, Interleukin-6; D014407:Tumor Cells, Cultured
chemical_list: D017077:Culture Media, Conditioned; D004273:DNA, Neoplasm; D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6