REGULATION OF BONE-MARROW STROMAL CELL-DIFFERENTIATION BY CYTOKINES WHOSE RECEPTORS SHARE THE GP130 PROTEIN

The bone marrow stroma consists of a heterogeneous population of cells which participate in osteogenic, adipogenic, and hematopoietic events . The murine stromal cell line, BMS2, exhibits the adipocytic and oste oblastic phenotypes in vitro. BMS2 differentiation was examined in res ponse to cytokines which share the gp130 signal transducing protein wi thin their receptor complex. Four of the cytokines (interleukin 6, int erleukin 11, leukemia inhibitory factor, and oncostatin M) inhibited h ydrocortisone-induced adipocyte differentiation in a dose dependent ma nner based on lipid accumulation and lipoprotein lipase enzyme activit y. Inhibition occurred only when the cytokines were present during the initial 24 h of the induction period; after 48 h, their effects were diminished. Likewise, these cytokines increased alkaline phosphatase e nzyme activity twofold in preadipocyte BMS2 cells. Both leukemia inhib itory factor and oncostatin M induced early active gene expression in resting preadipocyte BMS2. cells and decreased the steady state mRNA l evel of a unique osteoblastic gene marker, osteocalcin. A fifth cytoki ne whose receptor complex shares the gp130 protein, ciliary neurotroph ic factor, did not significantly regulate stromal cell differentiation when added by itself. However, with the addition of a missing compone nt of its receptor complex, ciliary neurotrophic factor receptor cw pr otein, this cytokine also inhibited BMS2 adipogenesis. Together, these data indicate that the cytokines whose receptors share the gp130 prot ein can modulate stromal cell commitment to the adipocyte and osteobla st differentiation pathways. (C) 1991 Wiley-Liss, Inc.