Zhang Li-Yan, Xue Hao-Gang, Chen Ji-Ying, Chai Wei, Ni Ming
Department of Orthopedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China; First Department of Orthopedics, The Affiliated Hospital of Beihua University, Jilin, Jilin 132001, P.R. China.
First Department of Orthopedics, The Affiliated Hospital of Beihua University, Jilin, Jilin 132001, P.R. China.
Exp Ther Med. 2016 May;11(5):1853-1858. doi: 10.3892/etm.2016.3120. Epub 2016 Mar 2.
Genistein is a soy isoflavone that exists in the form of an aglycone. It is the primary active component in soy isoflavone and has a number of biological activities (anti-inflammatory and anti-oxidative). However, the specific effect of genistein on human bone marrow mesenchymal stem cells (BMSCs) remains unclear. In the present study, the mechanism underlying the effect of genistein on the suppression of BMSC adipogenic differentiation and the enhancement of osteogenic potential was investigated using an MTT assay. It was observed that genistein significantly increased BMSC cell proliferation in a time- and dose-dependent manner (P<0.01). In addition, reverse transcription-quantitative polymerase chain reaction revealed that genistein significantly inhibited the expression of runt-related transcription factor 2 (Runx2), type I collagen (Col I) and osteocalcin (OC; P<0.01). Furthermore, 20 µm genistein significantly inhibited the activity of alkaline phosphatase (ALP) and increased the activity of triglycerides (TGs) increased (P<0.01) as determined by an enzyme-linked immunosorbent assay. Finally, western blotting revealed that BMSC pretreatment with 20 µm genistein significantly increased peroxisome proliferator-activated receptor γ (PPARγ) protein expression (P<0.01). This suggests that the downregulation of PPARγ may significantly reduce the effect of genistein on cell proliferation, suppress the expression of Runx2, Col I and OC mRNA, and reduce ALP and promote TG activity in BMSCs. Thus, the results of the present study conclude that genistein induces adipogenic differentiation in human BMSCs and suppresses their osteogenic potential by upregulating the expression of PPARγ. In conclusion, genistein may be a promising candidate drug for treatment against osteogenesis.
染料木黄酮是一种以苷元形式存在的大豆异黄酮。它是大豆异黄酮中的主要活性成分,具有多种生物活性(抗炎和抗氧化)。然而,染料木黄酮对人骨髓间充质干细胞(BMSCs)的具体作用仍不清楚。在本研究中,使用MTT法研究了染料木黄酮抑制BMSC成脂分化和增强成骨潜能作用的潜在机制。观察到染料木黄酮以时间和剂量依赖性方式显著增加BMSC细胞增殖(P<0.01)。此外,逆转录定量聚合酶链反应显示,染料木黄酮显著抑制矮小相关转录因子2(Runx2)、I型胶原(Col I)和骨钙素(OC)的表达(P<0.01)。此外,通过酶联免疫吸附测定法测定,20µm染料木黄酮显著抑制碱性磷酸酶(ALP)活性,并使甘油三酯(TGs)活性增加(P<0.01)。最后,蛋白质印迹法显示,用20µm染料木黄酮预处理BMSC可显著增加过氧化物酶体增殖物激活受体γ(PPARγ)蛋白表达(P<0.01)。这表明PPARγ的下调可能显著降低染料木黄酮对细胞增殖的作用,抑制Runx2、Col I和OC mRNA的表达,并降低BMSCs中的ALP活性和促进TG活性。因此,本研究结果得出结论,染料木黄酮通过上调PPARγ的表达诱导人BMSCs成脂分化并抑制其成骨潜能。总之,染料木黄酮可能是一种有前景的抗骨生成治疗候选药物。