Lysyl oxidase (LOX) is required for the formation of bone collagen cross-links. Inactivation of the LOX gene in osteoblasts by DNA methylation and JAK signaling has been reported to cause loss of cross-links and an increased risk of fractures. Tocotrienols (T3s) have proven benefits on bone strength, but their potential effects on LOX remain largely unknown. Thus, the present study investigates the in vitro effects of T3s on LOX expression in human osteoblastic MG-63 cells. Results indicated that Tocotrienol-Rich Fraction (TRF), the δ-T3 rich oil extracted from Annatto was the most effective and significantly increased LOX expression. TRF treatment decreased de-novo methyltransferases (DNMTs), DNMT3A and DNMT3B levels. In addition, TRF significantly inhibited JAK2 activation and decreased expression of Fli1, a transcription factor of DNMTs. We conclude that TRF induced an increase in LOX expression via inhibition of de-novo methylation and reduction of Fli1 expression by the inactivation of JAK2.Abbreviations: CpG: cytosine-guanine dinucleotide; DNMT: DNA methyltransferase; Fli1: friend leukemia virus integration 1; JAK: janus kinase; LOX: lysyl oxidase; PCR: polymerase chain reaction; STAT: signal transducers and activators of transcription; T3s: tocotrienols; TPs: tocopherols; TRF: Tocotrienol-Rich Fraction.

中文翻译：

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来自胭脂红的富含生育三烯酚的部分改善了人成骨细胞MG-63细胞中赖氨酰氧化酶的表达。

骨胶原交联的形成需要赖氨酰氧化酶（LOX）。据报道，通过DNA甲基化和JAK信号使成骨细胞中的LOX基因失活会导致交联丢失并增加骨折风险。生育三烯酚（T3s）对骨骼强度有好处，但对LOX的潜在影响仍未知。因此，本研究研究了T3对人成骨细胞MG-63细胞中LOX表达的体外作用。结果表明，从安纳托提取的富含δ-T3的生育三烯酚富集馏分（TRF）是最有效的并且显着增加了LOX表达。TRF治疗降低了新甲基转移酶（DNMT），DNMT3A和DNMT3B的水平。此外，TRF显着抑制JAK2活化并降低DNMTs转录因子Fli1的表达。我们得出的结论是，TRF通过抑制de-novo甲基化和通过灭活JAK2降低Fli1表达来诱导LOX表达增加。缩写：CpG：胞嘧啶-鸟嘌呤二核苷酸；DNMT：DNA甲基转移酶；Fli1：朋友白血病病毒整合1；JAK：janus激酶；LOX：赖氨酰氧化酶；PCR：聚合酶链反应；STAT：信号转导子和转录激活子；T3s：生育三烯酚；TP：生育酚；TRF：富含生育三烯酚的馏分。信号转导子和转录激活子；T3s：生育三烯酚；TP：生育酚；TRF：富含生育三烯酚的馏分。信号转导子和转录激活子；T3s：生育三烯酚；TP：生育酚；TRF：富含生育三烯酚的馏分。