Interleukin‐6 antisense deoxyoligonucleotides inhibit bone resorption by giant cells from human giant cell tumors of bone

Sakamuri V. Reddy, Shunji Takahashi, Mark Dallas, Ronald E. Williams, Leonard Neckers, G. David Roodman

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Abstract

The effects of antisense constructs to IL‐6 on the bone‐resorbing capacity of purified giant cells from giant cell tumors of bone were examined to further define the role of IL‐6 in human osteoclastic bone resorption. In addition, we wanted to determine the utility of antisense constructs to cytokines produced by osteoclasts as probes to identify the molecular events responsible for the bone‐resorptive process. Giant cells were cultured on sperm whale dentin for 24 h in the presence of fluoresceinated antisense or scrambled antisense deoxyoligonucleotides complementary to IL‐6 mRNA. The giant cells actively incorporated these oligonucleotides, as evidenced by their intense fluorescence. The number of resorptive lacunae formed and the area of the dentin resorbed were significantly decreased in cultures of giant cells treated with antisense IL‐6 constructs compared with control cultures treated with scrambled antisense constructs to IL‐6 (60 ± 13 versus 12 ± 6 lacunae and 1.2 ± 0.3 versus 0.26 ± 0.1 × 105 μm2). IL‐6 levels in conditioned media from giant cell cultures treated with IL‐6 antisense constructs were fourfold lower than those in control media obtained from giant cells treated with scrambled antisense constructs to IL‐6. These data confirm the capacity of IL‐6 antisense oligomers to block IL‐6 production by these cells. These observations show that IL‐6 plays an important role in the bone‐resorptive process of human osteoclasts and suggest that antisense constructs to cytokines produced by bone cells may be useful for determining the molecular events occurring during bone resorption.

Original languageEnglish (US)
Pages (from-to)753-757
Number of pages5
JournalJournal of Bone and Mineral Research
Volume9
Issue number5
DOIs
StatePublished - May 1994

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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