Hong Liu, Sultana Habiba, Paulius Karina, Zhang Guoquan
Department of Orthodontics, University of Illinois at Chicago, IL, USA.
J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):180-5. doi: 10.1016/j.jsbmb.2009.02.001. Epub 2009 Feb 13.
Bone marrow mesenchymal stem cells (MSCs) are considered a potential cell source for stem cell-based bone tissue engineering. However, noticeable limitations of insufficient supply and reduction of differentiation potential impact the feasibility of their clinical application. This study investigated the in vitro function of steroids and gender differences on the proliferation and differentiation of rat MSCs. Bone marrow MSCs of age-matched rats were exposed to proliferation and osteogenic differentiation media supplements with various concentrations of 17beta-estradiol (E2) and dexamethasone. Cell proliferation was measured by MTS assay; osteogenic markers and steroid-associated growth factors and receptors were evaluated by ELISA and real-time PCR. The results revealed that supplements of E2 and dexamethasone increase MSC proliferation in a biphasic manner. The optimal dose and interaction of steroids required to improve MSC proliferation effectively varied depending on the gender of donors. Supplementation of E2 effectively improves osteogenic differentiation markers including ALP, osteocalcin and calcium levels for MSCs isolated from both male and female donors. The mRNA of TGF-beta1 and BMP-7 are also up-regulated. However, effective doses to maximally improve osteogenic potentials and growth factors for MSCs are different between male and female donors. The relationship between steroid receptors, osteogenic markers and cytokines are also varied by genders. The outcomes of the present study strongly indicate that steroids potentially function as an effective modulator to improve the capacity of MSCs in bone regeneration. It provides crucial information for improving and optimizing MSCs for future clinical application of bone regeneration.
骨髓间充质干细胞（MSCs）被认为是基于干细胞的骨组织工程的潜在细胞来源。然而，供应不足和分化潜能降低等明显局限性影响了其临床应用的可行性。本研究调查了类固醇的体外功能以及性别差异对大鼠MSCs增殖和分化的影响。将年龄匹配的大鼠的骨髓MSCs暴露于含有不同浓度17β-雌二醇（E2）和地塞米松的增殖和成骨分化培养基补充剂中。通过MTS测定法测量细胞增殖；通过ELISA和实时PCR评估成骨标志物以及与类固醇相关的生长因子和受体。结果显示，E2和地塞米松补充剂以双相方式增加MSCs增殖。有效改善MSCs增殖所需的类固醇的最佳剂量和相互作用因供体性别而异。补充E2可有效改善从雄性和雌性供体分离的MSCs的成骨分化标志物，包括碱性磷酸酶（ALP）、骨钙素和钙水平。转化生长因子-β1（TGF-β1）和骨形态发生蛋白-7（BMP-7）的mRNA也上调。然而，最大程度提高MSCs成骨潜能和生长因子的有效剂量在雄性和雌性供体之间有所不同。类固醇受体、成骨标志物和细胞因子之间的关系也因性别而异。本研究结果强烈表明，类固醇可能作为一种有效的调节剂来提高MSCs在骨再生中的能力。它为改进和优化MSCs以用于未来骨再生的临床应用提供了关键信息。
