Suppression of T1-receptor expression by antisense RNA abrogates differentiation of osteogenic osteosarcoma cells

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.