scholarly journals The Phytoestrogen Genistein Enhances Osteogenesis and Represses Adipogenic Differentiation of Human Primary Bone Marrow Stromal Cells

Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 848-859 ◽  
Author(s):  
M. Heim ◽  
O. Frank ◽  
G. Kampmann ◽  
N. Sochocky ◽  
T. Pennimpede ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Adipogenic Differentiation ◽  
Marrow Stromal Cells ◽  
Marker Genes ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Genistein Treatment ◽  
17Β Estradiol

Abstract In the present study, we investigated the role of the phytoestrogen genistein and 17β-estradiol in human bone marrow stromal cells, undergoing induced osteogenic or adipogenic differentiation. Profiling of estrogen receptors (ERs)-α, -β1, -β2, -β3, -β4, -β5, and aromatase mRNAs revealed lineage-dependent expression patterns. During osteogenic differentiation, the osteoblast-determining core binding factor-α1 showed a progressive increase, whereas the adipogenic regulator peroxisome proliferator-activated receptor γ (PPARγ) was sequentially decreased. This temporal regulation of lineage-determining marker genes was strongly enhanced by genistein during the early osteogenic phase. Moreover, genistein increased alkaline phosphatase mRNA levels and activity, the osteoprotegerin:receptor activator of nuclear factor-κB ligand gene expression ratio, and the expression of TGFβ1. During adipogenic differentiation, down-regulation in the mRNA levels of PPARγ and CCAAT/enhancer-binding protein-α at d 3 and decreased lipoprotein lipase and adipsin mRNA levels at d 21 were observed after genistein treatment. This led to a lower number of adipocytes and a reduction in the size of their lipid droplets. At d 3 of adipogenesis, TGFβ1 was strongly up-regulated by genistein in an ER-dependent manner. Blocking the TGFβ1 pathway abolished the effects of genistein on PPARγ protein levels and led to a reduction in the proliferation rate of precursor cells. Overall, genistein enhanced the commitment and differentiation of bone marrow stromal cells to the osteoblast lineage but did not influence the late osteogenic maturation markers. Adipogenic differentiation and maturation, on the other hand, were reduced by genistein (and 17β-estradiol) via an ER-dependent mechanism involving autocrine or paracrine TGFβ1 signaling.

scholarly journals Effect of Increasing Doses ofγ-Radiation on Bone Marrow Stromal Cells Grown on Smooth and Rough Titanium Surfaces

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Bo Huang ◽  
Mengkai Guang ◽  
Jun Ye ◽  
Ping Gong ◽  
Hua Tang
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Adipogenic Differentiation ◽  
Marrow Stromal Cells ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Alizarin Red ◽  
Titanium Surfaces

Radiation therapy for oral and maxillofacial tumors could damage bone marrow stromal cells (BMSCs) in jaw, which caused dental implant failure. However, how radiation affects BMSCs on SLA (sandblasted with large-grits, acid-etched) surfaces is still unknown. The aim of this study was to investigate effect of different dose ofγ-radiation on BMSCs on SLA and PT (polished titanium) surfaces. Rat BMSCs were radiated with 2, 4, and 8 Gyγ-radiation and then seeded on both surfaces. Cell adhesion, spreading, and proliferation were tested. The osteogenesis and the adipogenesis ability were examined by Alizarin-Red and Oil-Red staining, respectively. Real-time PCR was performed to detect osteogenic (osteocalcin, OCN; runt-related transcription factor 2, Runx2) and adipogenic (peroxisome proliferator-activated receptor gamma, PPARγ) gene expression at days 7 and 14 postirradiation. Results showed thatγ-radiation reduced cell proliferation, adhesion, spreading, and osteogenic differentiation. 2 Gy radiation promoted adipogenic differentiation, but it was significantly decreased when dosage reached 4 Gy. In conclusion, results suggest thatγ-radiation influenced BMSCs behaviors in a dosage-dependent manner except adipogenic differentiation, low dose promoted it, and high dose inhibited it. This effect was influenced by surface characteristics, which may explain the different failure rate of various implants in patients after radiation.

Asiatic Acid Inhibits Adipogenic Differentiation of Bone Marrow Stromal Cells

2013 ◽  
Vol 68 (2) ◽  
pp. 437-442 ◽  
Author(s):  
Zheng-Wei Li ◽  
Cheng-dong Piao ◽  
Hong-Hui Sun ◽  
Xian-Sheng Ren ◽  
Yun-Shen Bai
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Adipogenic Differentiation ◽  
Marrow Stromal Cells ◽  
Asiatic Acid

scholarly journals 1,25-Dihydroxyvitamin D3 stimulates the production of insulin-like growth factor-binding proteins-2, -3 and -4 in human bone marrow stromal cells

2001 ◽  
pp. 549-557 ◽  
Author(s):  
M Kveiborg ◽  
A Flyvbjerg ◽  
EF Eriksen ◽  
M Kassem
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Binding Proteins ◽  
Marrow Stromal Cells ◽  
Mrna Levels ◽  
Dihydroxyvitamin D3 ◽  
Igf System ◽  
Proliferation And Differentiation ◽  
Igfbp 3

BACKGROUND: 1,25-Dihydroxyvitamin D3 (calcitriol) inhibits proliferation and stimulates differentiation of multiple cell types, including osteoblasts. Human (h) bone marrow stromal cells (MSCs) are a homogenous non-hematopoietic population of cells present in the bone marrow and exhibit a less differentiated osteoblastic phenotype. The IGF system, including IGFs-I, and -II and IGF binding proteins (IGFBPs), plays an important role in osteoblast cell proliferation and differentiation. OBJECTIVE: To examine the pattern of expression of the IGF system in hMSCss and its regulation by calcitriol. METHODS AND RESULTS: hMSCs express mRNA of both IGFs-I, and -II and IGFBPs-1 to -6 as shown by RT-PCR and northern blot analysis. As assessed by western ligand blotting (WLB) and western immmunoblot analysis, hMSCs secrete 38-42 kDa IGFBP-3, 24-28 kDa IGFBP-4 and a 33 kDa IGFBP-2. Calcitriol (dose range 10-10 mol/l) exerted no consistent dose-dependent effects on either IGF-I or IGF-II mRNA levels. In contrast, calcitriol treatment increased steady-state mRNA levels of IGFBPs-2, -3 and -4, but had no effect on IGFBP-5 or -6. Similarly, calcitriol increased the secretion of IGFBPs-2, -3 and -4 as determined by WLB. We found no detectable basal IGFBP-3 or IGFBP-4 protease activities in the absence or presence of calcitriol treatment. CONCLUSIONS: Our results demonstrate that hMSCs expressed a distinct pattern of IGFs and IGFBPs that may be related to their stage of differentiation. The observed increase in production of IGFBPs-2, -3 and -4 by hMSCs upon treatment with calcitriol may be an important mechanism mediating the effects of calcitriol on MSC proliferation and differentiation.

HSP70 Induces IL-6 in Stromal Cells and Stat-3 Activation in Myeloma Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3353-3353
Author(s):  
Ramadevi Nimmanapalli ◽  
Elvira Gerbino ◽  
William S. Dalton ◽  
Melissa Alsina
Keyword(s):  
Bone Marrow ◽  
Heat Shock ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Mammalian Cells ◽  
Marrow Stromal Cells ◽  
Hsp70 Expression ◽  
High Dose ◽  
Dependent Manner ◽  
Myeloma Cells

Abstract Multiple myeloma (MM) is characterized by the clonal proliferation of malignant plasma cells that accumulate preferentially in the bone marrow. In spite of high dose chemotherapy and novel targeted therapies this disease remains incurable with a median survival of 3–6 years mainly because of the emergence of drug resistance. Improved survival requires new strategies to prevent relapse. Heat shock proteins (HSPs) are a super family of highly conserved proteins, which are induced in plant, yeast, bacterial and mammalian cells in response to an array of physiological and environmental stress cues. Among heat shock protein families, HSP70 is one of the most highly conserved and is the only protein expressed in response to cellular stress. Exogenous HSP70 has been demonstrated to act as a cytokine to human monocytes by stimulating rapid calcium influx, activating nuclear factor (NF)-kB and up-regulating the expression of IL-1b, IL-6 and tumor necrosis factor alpha (TNF-a) (Asea A et al., 2000). Adhesion of myeloma cells to bone marrow stromal cells mediates IL-6 secretion and tumor cell proliferation in part mediated by STAT-3 activation (Cheung WC et al., 2001). We have shown that adhesion of myeloma cells to bone marrow stromal cells enhances IL-6 secretion by stromal cells and HSP70 secretion by myeloma cells. When we inhibited the HSP70 expression using either KNK437 (HSF-1 inhibitor) or RNAi to HSP70, IL-6 secretion by stromal cells as well as activation of STAT-3 in myeloma cells was inhibited in dose-dependent manner. These results suggest that HSP70 released from myeloma cells is enhancing IL-6 secretion from stromal cells. Incubation of stromal cells with recombinant HSP70 did not enhance IL-6 secretion in stromal cells suggesting that some other soluble factor released from myeloma cells cooperates with HSP70 to enhance IL-6 secretion by stromal cells, We examined whether HSP70 can modulate IL-6 mediated STAT-3 activation by stimulating 8226 cells with IL-6 in the presence or absence of KNK437 and RNAi to HSP70 and measuring phospho-STAT-3 by western analysis. HSP70 inhibition attenuated IL-6 induced STAT-3 activity, but not ERK1/2 activity, indicating that HSP70 mediated IL-6 signaling is very specific to STAT-3. The signal transduction cascade by which HSP70 induces IL-6 secretion and the mechanism by which HSP70 mediates IL-6 induced STAT-3 activity are currently under investigation.

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