Steroid regulation of proliferation and osteogenic differentiation of bone marrow stromal cells: A gender difference

Department of Orthodontics, University of Illinois at Chicago, IL, USA.
The Journal of steroid biochemistry and molecular biology (Impact Factor: 3.63). 05/2009; 114(3-5):180-5. DOI: 10.1016/j.jsbmb.2009.02.001
Source: PubMed


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.

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    • "Among the 3 types of estrogen, i.e. 17β-estradiol (E2), estron, and estriol, E2, which is secreted in the ovarium of normally cycling adult women, has the highest estrogenic potent [Eastel, 2005]. In recent studies, it was demonstrated that: (i) E2 supplementation effectively stimulates the proliferative capacity of mesenchymal stem cells (MSCs) [Qu et al., 1998; Zhou et al., 2001; Hong et al., 2009], (ii) E2 inhibits MSC senescence via the upregulation of telomerase [Hong et al., 2009], and (iii) E2 improves the osteogenic and adipogenic differentiation of MSCs [Zhou et al., 2001; Hong et al., 2006, 2007]. Adipose tissue represents an abundant and accessible source of adult stem cells that can be differentiated into osteogenic [Im et al., 2005; Shi et al., 2005; Weinzierl et al., 2006; Qu et al., 2007], adipogenic [Gimble and Guilak, 2003; Qu et al., 2007], chondrogenic [Huang et al., 2004; Qu et al., 2007], and myogenic cells in a lineage-specific culture medium [Zuk et al., 2001; Rada et al., 2009]. "
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    ABSTRACT: The aim of this study was to develop a 17β-estradiol (E2)-releasing scaffold-nanoparticle system in order to promote osteogenic differentiation of rat adipose tissue-derived mesenchymal stem cells (AdMSCs) for bone tissue regeneration. E2-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles with a diameter of ∼240 nm were produced via an emulsion-diffusion-evaporation method. Because of its higher encapsulation efficiency (54%), PLGA, which has a 65:35 composition, was chosen for the preparation of nanoparticles. Chitosan-hydroxyapatite (HA) scaffolds in macroporous structures with interconnected pores were prepared by combining microwave irradiation and gas-foaming techniques. PLGA nanoparticles were loaded onto scaffolds in 2 ways: via embedding after scaffold fabrication and during fabrication. While 100% of the loaded E2 was released during 55 days from scaffolds loaded by embedding, a controlled release behavior of E2 was observed over 135 days in scaffolds loaded during manufacture. The results of cell culture studies indicated that the controlled delivery of E2 from PLGA nanoparticles loaded on chitosan-HA scaffolds had a significant effect on the osteogenic differentiation of AdMSCs. © 2014 S. Karger AG, Basel.
    Cells Tissues Organs 08/2014; 199(1). DOI:10.1159/000362362 · 2.14 Impact Factor
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    • "Cell-size related growth rate was also observed by Estes et al. (2008), who reported a similar effect in hASCs with an expansion medium containing FGF-2, EGF (epidermal growth factor) and TGFb, which is also supported by observations in other adult stem cells, such as bone marrow MSCs (Sekiya et al., 2002). On the other hand, the addition of Dex did not promote cell proliferation, nor was there a synergistic effect in combination with FGF-2, which is contrary to previous studies using MSCs (Hong et al., 2009; Xiao et al., 2010). This may be attributable to differences in cell type, donor species, or the passage number of the cells. "
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    ABSTRACT: hASCs [human ASCs (adipose derived stromal cells)] proliferate more rapidly in the presence of basic FGF-2 (fibroblast growth factor-2) and Dex (dexamethasone). We have examined the effects of expanding hASCs in media containing these two factors on their chondrogenic differentiation potential. Results show that the addition of FGF-2 and Dex to the expansion medium does not remarkably alter the chondrogenic potential of the cells induced by BMP-6 (bone morphogenetic protein-6), based on chondrogenic gene expression, sGAG (sulfated glycosaminoglycan) accumulation and immunohistochemical observation. This is in direct contrast to previously reported promotion of the osteogenic and adipogenic potential of hASCs by these two factors. Therefore, an expansion medium containing FGF-2, with or without Dex, is appropriate for the fast expansion of hASCs without compromising chondrogenic potential.
    Cell Biology International 02/2012; 36(7):611-5. DOI:10.1042/CBI20110503 · 1.93 Impact Factor
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    • "Other work documented that at 10 −7 M Dex suppressed the osteogenic differentiation of hMSCs and produced a shift to adipogenic differentiation (Wang et al., 2000; Chang et al., 2006). For MSCs of rat origin, it was found that at 10 −6 M Dex suppressed proliferation, while at 10 −10 M Dex increased proliferation (Hong et al., 2009). For hMSCs, depending on the dosage, Dex can induce differentiation (Muraglia et al., 2000) or proliferation (Awad et al., 2003; Both et al., 2007). "
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    ABSTRACT: Human mesenchymal stem cells (hMSCs) can form various mesodermal tissues when grown under appropriate conditions. Dexamethasone (Dex) is regularly used to stimulate the osteogenic potential of hMSCs and it has recently been reported to increase the cell expansion rate. In this study we have investigated the effect of low-dose Dex treatment (10(-8) M) on the multipotency of expanded hMSCs, using histological, biochemical and molecular biological techniques. Early passage (P2-3) and late passage (P6) cells were positive (>90%) for mesenchymal adhesion cell markers (CD105/CD29/CD44/CD166/CD90) and negative (<10%) for haematopoietic markers (CD34/CD45/CD14). Dex did not change the overall expression pattern of these cell surface markers. Expanded hMSCs gave rise to specialized cell lineages when grown in differentiation-promoting medium. Depending on the donor, Dex treatment improved the potency for osteogenic, adipogenic and chondrogenic differentiation of expanded hMSCs. Dex also prevented the loss of proliferative potential of hMSCs upon sequential passaging and the loss of the typical hMSCs surface phenotype. hMSCs gene expression analysis showed that low-dose Dex negatively regulated transcription of genes correlated with apoptosis and differentiation, and positively regulated genes associated with cell proliferation. In conclusion, the collective data argue that low-dose Dex preserves the stemness of hMSCs during repeated passaging, as indicated by the maintenance of the stem cell phenotype, proliferative capacity and multi-lineage differentiation potential.
    Journal of Tissue Engineering and Regenerative Medicine 07/2010; 4(5):374-86. DOI:10.1002/term.250 · 5.20 Impact Factor
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