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

REGULATION OF BONE-MARROW STROMAL CELL-DIFFERENTIATION BY CYTOKINES WHOSE RECEPTORS SHARE THE GP130 PROTEIN
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DOI:
10.1002/jcb.240540113
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发表时间:
1994-01-01
影响因子:
4
通讯作者:
HILL, MR
HILL, MR
中科院分区:
生物学2区
文献类型:
--
作者:
GIMBLE, JM;WANKER, F;HILL, MR

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骨髓基质由参与成骨、脂肪和造血事件的异质细胞群组成。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。BMS2分化在细胞因子的响应中被检测,细胞因子在其受体复合体中共享gp130信号转导蛋白。四种细胞因子(白细胞介素6、白细胞介素11、白血病抑制因子和抑癌素M)以剂量依赖的方式抑制氢化可的松诱导的脂肪细胞分化,这种方式基于脂质积累和脂蛋白脂肪酶活性。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;48 h后,其作用减弱。同样,这些细胞因子使前脂肪细胞BMS2细胞的碱性磷酸酶活性增加了两倍。白血病抑制因子和抑癌素M均可诱导静息前脂肪细胞BMS2的早期活性基因表达。并降低了一种独特的成骨细胞基因标志物骨钙素的稳态mRNA水平。第五种细胞因子,其受体复合物共享gp130蛋白,纤毛神经营养因子,当单独添加时,不显著调节基质细胞分化。然而,随着其受体复合体纤毛神经营养因子受体cw蛋白缺失组分的加入,该细胞因子也抑制BMS2脂肪生成。总之,这些数据表明,受体共享gp130蛋白的细胞因子可以调节基质细胞对脂肪细胞和成骨细胞分化途径的承诺。(C) 1991 Wiley-Liss, Inc。
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 cw 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. (C) 1991 Wiley-Liss, Inc.