Osteogenic imprinting upstream of marrow stromal cell differentiation

Five spontaneously transformed cell lines were established from a populatio n of murine bone marrow stromal cells (BMSCs) and the expression profiles o f phenotype-characteristic genes, patterns of in vitro differentiation, and osteogenic capacity after in vivo transplantation were determined for each . All the clones expressed stable levels of cbfa1, the osteogenic "master" gene, whereas the levels of individual phenotypic mRNAs were variable withi n each, suggestive of both maturational and phenotypic plasticity in vitro. Varying levels of collagen type I and alkaline phosphatase (AP) were expre ssed in all the clonal lines. The clonal lines with proven in vivo osteogen ic potential (3 out of 5) had a high proliferation rate and expressed bone sialoprotein (BSP), whereas the two nonosteogenic clones proliferated more slowly and never expressed BSP. Bone nodules were only observed in 2 out of 3 of the osteogenic lines, and only 1 out of three formed cartilage-like m atrix in vitro. There was no evidence of chondrogenesis in the nonosteogeni c lines. By contrast, LPL was expressed in two osteogenic and in two nonost eogenic lines. These results demonstrate the presence of multipotential and restricted progenitors in the murine stromal system, cbfa1, collagen type I, and AP expression were common to all, and therefore presumably early, ba sic traits of stromal cell lines that otherwise significantly differ with r espect to growth and differentiation potential. This finding suggests that an osteogenic imprinting lies upstream of diversification, modulation, and restriction of stromal cell differentiation potential. Published 2000 Wiley -Liss, Inc.