The PPARgamma-selective ligand BRL-49653 differentially regulates the fate choices of rat calvaria versus rat bone marrow stromal cell populations
The PPARgamma-selective ligand BRL-49653 differentially regulates the fate choices of rat calvaria versus rat bone marrow stromal cell populations
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DOI：
10.1186/1471-213x-8-71
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发表时间：
2008-07-14
影响因子：
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通讯作者：
Aubin, Jane E.
中科院分区：
文献类型：
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作者：
Hasegawa, Takuro;Oizumi, Kiyoshi;Aubin, Jane E.
背景：成骨细胞和脂肪细胞源自共同的间充质祖细胞，并且通过某些实验操作和在某些疾病（即骨质疏松症）中观察到两种谱系的表达之间存在反向关系，但反向关系背后的细胞途径和发育阶段仍在积极研究中。为了确定哪些前体间充质细胞类型可以分化为脂肪细胞，我们比较了 BRL-49653 (BRL)（一种过氧化物酶体增殖物激活受体 (PPAR)gamma（脂肪生成的主要转录因子）的选择性配体）对两种不同成骨细胞培养模型（大鼠骨髓 (RBM) 与胎鼠颅骨 (RC) 细胞系统）中骨/脂肪生成的影响。结果：BRL 增加了在两种培养模型中，脂肪细胞和相应的标记物表达，例如脂蛋白脂肪酶、脂肪酸结合蛋白（aP2）和脂肪素，但仅在 RBM 培养物中影响成骨细胞生成，其中骨结节形成和成骨细胞标记物（例如，成骨细胞标记物）相互减少。例如，观察到骨桥蛋白、碱性磷酸酶 (ALP)、骨唾液蛋白和骨钙素，但在 RC 细胞培养物中未观察到。尽管在未用 BRL 处理的 RC 培养物中在组织学上检测不到脂肪细胞，但 RC 细胞在成骨细胞发育过程中表达 PPAR 和 CCAAT/增强子结合蛋白 (C/EBP) mRNA，并且 BRL 会增加它们的表达。一些单细胞来源的 BRL 处理的成骨 RC 集落不仅用 ALP/von Kossa 染色，还用油红 O 染色，并共表达成熟脂肪细胞标记物 adipsin 和成熟成骨细胞标记物 OCN，以及 PPAR 和 C/EBP mRNA。 结论：数据表明，BRL 改变基质 (RBM) 与颅骨 (RC) 细胞群中前体细胞命运选择的能力存在明显差异。脂肪细胞的募集可以从多个前体细胞池中发生（定向前脂肪细胞池、多能/双能骨脂肪祖细胞池以及骨祖细胞或成骨细胞转化为脂肪细胞（转分化或可塑性））。他们还表明了 PPAR 激活之外的机制。其配体需要改变定型骨祖细胞和/或成骨细胞向脂肪细胞的命运。
Background: Osteoblasts and adipocytes are derived from a common mesenchymal progenitor and an inverse relationship between expression of the two lineages is seen with certain experimental manipulations and in certain diseases, i.e., osteoporosis, but the cellular pathway(s) and developmental stages underlying the inverse relationship is still under active investigation. To determine which precursor mesenchymal cell types can differentiate into adipocytes, we compared the effects of BRL-49653 (BRL), a selective ligand for peroxisome proliferators-activated receptor (PPAR)gamma, a master transcription factor of adipogenesis, on osteo/adipogeneis in two different osteoblast culture models: the rat bone marrow (RBM) versus the fetal rat calvaria (RC) cell system.Results: BRL increased the number of adipocytes and corresponding marker expression, such as lipoprotein lipase, fatty acid-binding protein (aP2), and adipsin, in both culture models, but affected osteoblastogenesis only in RBM cultures, where a reciprocal decrease in bone nodule formation and osteoblast markers, e. g., osteopontin, alkaline phosphatase (ALP), bone sialoprotein, and osteocalcin was seen, and not in RC cell cultures. Even though adipocytes were histologically undetectable in RC cultures not treated with BRL, RC cells expressed PPAR and CCAAT/enhancer binding protein (C/EBP) mRNAs throughout osteoblast development and their expression was increased by BRL. Some single cell-derived BRL-treated osteogenic RC colonies were stained not only with ALP/von Kossa but also with oil red O and co-expressed the mature adipocyte marker adipsin and the mature osteoblast marker OCN, as well as PPAR and C/EBP mRNAs.Conclusion: The data show that there are clear differences in the capacity of BRL to alter the fate choices of precursor cells in stromal (RBM) versus calvarial (RC) cell populations and that recruitment of adipocytes can occur from multiple precursor cell pools (committed preadipocyte pool, multi-/bipotential osteo-adipoprogenitor pool and conversion of osteoprogenitor cells or osteoblasts into adipocytes (transdifferentiation or plasticity)). They also show that mechanisms beyond activation of PPAR. by its ligand are required for changing the fate of committed osteoprogenitor cells and/or osteoblasts into adipocytes.