3T3-L1 pre-adipocytes are used commonly to identify new adipogens, but this cell line has been shown to produce variable results. Here, potential adipogenic chemicals (identified in the ToxCast dataset using the Toxicological Priority Index) were tested for their ability to induce adipocyte differentiation in 3T3-L1 cells, OP9 cells and primary mouse bone marrow multipotent stromal cells (BM-MSC). Ten of the 36 potential adipogens stimulated lipid accumulation in at least one model (novel: fenthion, quinoxyfen, prallethrin, allethrin, pyrimethanil, tebuconzaole, 2,4,6-tris (tert-butyl)phenol; known: fentin, pioglitazone, 3,3′,5,5′-tetrabromobisphenol A). Only prallethrin and pioglitazone enhanced lipid accumulation in all models. OP9 cells were significantly more sensitive to chemicals known to activate PPARγ through RXR than the other models. Coordinate effects on adipocyte and osteoblast differentiation were investigated further in BM-MSCs. Lipid accumulation was correlated with the ability to stimulate expression of the PPARγ target gene, Plin1. Induction of lipid accumulation also was associated with reduction in alkaline phosphatase activity. Allethrin, prallethrin, and quinoxyfen strongly suppressed osteogenic gene expression. BM-MSCs were useful in coordinately investigating pro-adipogenic and anti-osteogenic effects. Overall, the results show that additional models should be used in conjunction with 3T3-L1 cells to identify a broader spectrum of adipogens and their coordinate effects on osteogenesis.

3T3-L1 前脂肪细胞通常用于识别新的脂肪原，但该细胞系已显示产生可变结果。在这里，潜在的成脂化学物质（使用毒理学优先指数在 ToxCast 数据集中确定）测试了它们在 3T3-L1 细胞、OP9 细胞和原代小鼠骨髓多能基质细胞 (BM-MSC) 中诱导脂肪细胞分化的能力。36 种潜在脂肪原中有 10 种刺激了至少一种模型中的脂质积累（新型：倍硫磷、喹氧芬、丙烯菊酯、丙烯菊酯、嘧霉胺、戊唑醇、2,4,6-三（叔丁基）苯酚；已知：芬丁、吡格列酮、3 ,3',5,5'-四溴双酚 A)。在所有模型中，只有丙烯菊酯和吡格列酮增强了脂质积累。与其他模型相比，OP9 细胞对已知通过 RXR 激活 PPARγ 的化学物质明显更敏感。在 BM-MSCs 中进一步研究了对脂肪细胞和成骨细胞分化的协调效应。脂质积累与刺激 PPARγ 靶基因表达的能力相关，普林1。脂质积累的诱导也与碱性磷酸酶活性的降低有关。Allethrin、prallethrin 和 quinoxyfen 强烈抑制成骨基因表达。BM-MSCs 可用于协调研究促脂肪生成和抗成骨作用。总体而言，结果表明，应将其他模型与 3T3-L1 细胞结合使用，以识别更广泛的脂肪原及其对成骨的协同作用。