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Suppression
of T1-Receptor Expression by Antisense RNA Abrogates Differentiation of
Osteogenic Osteosarcoma Cells |
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Anne Katrin
Werenskiold, Jörg Schmidt, Brigitte Rupp, Wolfgang Gössner, and
Heinz Höfler |
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Institut
für Pathologie (AKW, BR, HH), Technische Universität, D-81675
München, Germany; Institut für Molekulare Virologie (JS) and Institut
für Pathologie (WG, HH), GSF-Forschungszentrum für Umwelt und
Gesundheit, D-85764 Neuherberg, Germany |
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Soluble and membrane-associated
variants of the orphan T1-receptor, a homolog of interleukin-1 receptor
type I, are expressed in proliferating preosteoblasts in differentiating
bone. Recent evidence reveals that T1-receptor synthesis is retained in
osteogenic osteosarcoma cells. Here we report that the suppression of T1-receptor
expression by mouse osteosarcoma cells using a T1-antisense expression vector
results in the abrogation of the osteogenic potential of the tumor cells.
T1-antisense-expressing tumor cells formed anaplastic tumors in vivo and
failed to express the osteoblast-specific genes collagen type 1, alkaline
phosphatase, and osteocalcin when cultured in a 3-dimensional collagen type
I matrix in vitro. Suppression of T1-receptor synthesis did not affect the
expression of the essential bone cell-specific transcription factor AML3/CBFA1
in the osteosarcoma cells. These data provide the first evidence that T1-receptor
plays a key role in osteogenic differentiation. (Lab Invest, 79:529-536) |
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