Gimble J M, Wanker F, Wang C S, Bass H, Wu X, Kelly K, Yancopoulos G D, Hill M R
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
J Cell Biochem. 1994 Jan;54(1):122-33. doi: 10.1002/jcb.240540113.
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 osteoblastic phenotypes in vitro. BMS2 differentiation was examined in response to cytokines which share the gp130 signal transducing protein within their receptor complex. Four of the cytokines (interleukin 6, interleukin 11, leukemia inhibitory factor, and oncostatin M) inhibited hydrocortisone-induced adipocyte differentiation in a dose dependent manner based on lipid accumulation and lipoprotein lipase enzyme activity. 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 enzyme activity twofold in preadipocyte BMS2 cells. Both leukemia inhibitory factor and oncostatin M induced early active gene expression in resting preadipocyte BMS2 cells and decreased the steady state mRNA level of a unique osteoblastic gene marker, osteocalcin. A fifth cytokine whose receptor complex shares the gp130 protein, ciliary neurotrophic factor, did not significantly regulate stromal cell differentiation when added by itself. However, with the addition of a missing component of its receptor complex, ciliary neurotrophic factor receptor alpha protein, this cytokine also inhibited BMS2 adipogenesis. Together, these data indicate that the cytokines whose receptors share the gp130 protein can modulate stromal cell commitment to the adipocyte and osteoblast differentiation pathways.
骨髓基质由多种异质性细胞群体组成，这些细胞参与成骨、成脂和造血过程。小鼠基质细胞系BMS2在体外表现出脂肪细胞和成骨细胞表型。研究了BMS2对其受体复合物中共享gp130信号转导蛋白的细胞因子的分化反应。基于脂质积累和脂蛋白脂肪酶活性，其中四种细胞因子（白细胞介素6、白细胞介素11、白血病抑制因子和制瘤素M）以剂量依赖方式抑制氢化可的松诱导的脂肪细胞分化。仅当细胞因子在诱导期的最初24小时内存在时才会发生抑制作用；48小时后其作用减弱。同样，这些细胞因子使前脂肪细胞BMS2中的碱性磷酸酶活性增加了两倍。白血病抑制因子和制瘤素M均诱导静止前脂肪细胞BMS2中的早期活性基因表达，并降低独特的成骨细胞基因标志物骨钙素的稳态mRNA水平。其受体复合物共享gp130蛋白的第五种细胞因子睫状神经营养因子单独添加时对基质细胞分化没有显著调节作用。然而，添加其受体复合物的缺失成分睫状神经营养因子受体α蛋白后，这种细胞因子也抑制了BMS2的脂肪生成。总之，这些数据表明其受体共享gp130蛋白的细胞因子可以调节基质细胞向脂肪细胞和成骨细胞分化途径的定向分化。
