Genistein induces adipogenic differentiation in human bone marrow mesenchymal stem cells and suppresses their osteogenic potential by upregulating PPARγ

  • Authors:
    • Li‑Yan Zhang
    • Hao‑Gang Xue
    • Ji‑Ying Chen
    • Wei Chai
    • Ming Ni
  • View Affiliations

  • Published online on: March 2, 2016     https://doi.org/10.3892/etm.2016.3120
  • Pages: 1853-1858
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Abstract

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.

Introduction

Bone marrow mesenchymal stem cells (BMSCs) are fibrocyte-like stem cells that exist alongside hematopoietic stem cells within the marrow cavity. BMSCs are highly self-renewable with multipotential differentiation (1); they may develop into osteoblasts, chondrocytes and adipose cells through directional differentiation, and at present it is understood that all osteoblasts are derived from BMSCs (2).

Peroxisome proliferator-activated receptor γ (PPARγ) is a PPAR subtype that contributes towards the regulation of cell differentiation, proliferation and apoptosis (3,4). To date, it is understood that the PPARγ subtype is the primary regulator of fat differentiation, which serves a key regulatory role in the direction of BMSC differentiation (5). In the marrow cavity, osteoblasts and adipocytes are derived from BMSCs, and it is understood that there is an association between their expression levels (6). Previous studies demonstrate that PPARγ-mediated adipogenic differentiation of BMSCs directly affects the differentiation of osteoblasts (7,8). Osteoclasts are derived from hematopoietic stem cells in bone marrow, and are responsible for increased bone resorption and osteoporosis; this is demonstrated through an increase of fat in bone marrow cavities that occurs in every type of osteoporosis (9,10).

Soy isoflavone is a class 1 secondary metabolite that is formed during the growth of soybeans. In total, 12 types of natural isoflavones exist in soybeans, including daidzin, daidzein, genistin, genistein, glycitin and glycitein (11). Of these, genistein possesses the highest level of activity (12). Genistein possesses a number of bioactivities (13); it is an effective antioxidant, a protein tyrosine activating enzyme inhibitor and a phytoestrogen (14). In recent years, increasing evidence indicates that genistein may aid in the prevention and treatment of breast cancer, prostatic cancer, post-menopause syndrome, osteoporosis and angiocardiopathy (15,16). In the present study, the mechanisms underlying the effect of genistein on the suppression of human BMSC adipogenic differentiation and the enhancement of BMSC osteogenic potential were investigated.

Materials and methods

Reagents

Dulbeccos modified Eagles medium (DMEM) and fetal bovine serum (FBS) were provided by Gibco (Thermo Fisher Scientific, Inc., Waltham, MA, USA), and genistein (Fig. 1; ≥98%, high-performance liquid chromatography) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were provided by Sigma-Aldrich (St. Louis, MO, USA).

BMSC culture and identification

The use of animals in the present study was approved by the Animal Care and Use Committee of the Chinese People's Liberation Army General Hospital (Beijing, China). A total of 20 male and female Sprague-Dawley rats (age, 2–4 weeks; 100±10 g; male = 24, female = 24; purchased from Charles River Laboratories, Wilmington, MA, USA) were used to isolate marrow-derived BMSCs and were housed in an animal quarter (humidity, 60–70%; temperature, 23±1°C; 12-h light-dark cycle) with ad libitum access to food and water. Rats were sacrificed by cervical dislocation and BMSCs were isolated according to a previously described method (17). Briefly, bone marrow was flushed from the femur and tibia with saline, and placed into 25 cm2 flasks with DMEM supplemented with 10% FBS, 100 units penicillin and 100 µg-ml streptomycin (both purchased from Sigma-Aldrich), and was incubated at 37°C in a humidified atmosphere containing 5% CO2 for 1 day. Following the incubation period, nonadherent cells were removed and adherent cells were washed with phosphate-buffered saline (PBS; Sinopharm Chemical Reagent Co., Ltd., Shanghai, China). Next, adherent cells were incubated with DMEM for 2 h at 37°C and washed with PBS once they reached 80–90% confluence. The cells were detached using 0.25% trypsin (Nanjing Sunshine Biotechnology, Co., Ltd., Nanjing, China) and the remaining cells were incubated in new 25 cm2 flasks.

BMSCs were treated with genistein (0, 5, 10 and 20 µm) for 1, 2 or 3 days or GW9662 (1 mM; Invitrogen; Thermo Fisher Scientific, Inc.), a PPARγ inhibitor. BMSCs were then fixed using 5% pre-cooled paraformaldehyde (Sinopharm Chemical Reagent Co., Ltd.) for 10–15 min at 4°C, and cultured with hematoxylin and eosin staining (Invitrogen; Thermo Fisher Scientific, Inc.) for 10 min. Next, BMSCs were washed using tap and distilled water for 5–10 min. Stained BMSCs were dehydrated with 95% ethanol for 1–2 min and xylene (Shangbeijia Biological Technology Co., Ltd.) was applied for 5–10 min until transparent. BMSCs were analyzed using a microscope (TE2000; Nikon Corporation, Tokyo, Japan).

Grouping and cell proliferation assay

BMSCs were seeded in 96-well plates and incubated with different concentrations of genistein (0, 5, 10 and 20 µm) for 1, 2 and 3 days or GW9662 (1 mM). In the MTT cell proliferation assay, BMSCs were incubated with 20 µl MTT for 4 h at 37°C in a humidified atmosphere containing 5% CO2. Once the medium was removed, 150 µl dimethyl sulfoxide was added for 10 min at room temperature. The optical density was read at 570 nm (Epoch Microplate Spectrophotometer; BioTek Instruments, Inc., Winooski, VT, USA).

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of runt-related transcription factor 2 (Runx2), collagen type I (Col I) and osteocalcin (OC)

Following treatment with genistein, total RNA (1 µg) was extracted using TRIzol reagent (Invitrogen; Thermo Fisher Scientific, Inc.) and BMSC cDNA (1 µg) was transcribed using RT-PCR Quick Master Mix (Toyoba Co., Ltd., Dalian, China) according to the manufacturers protocol. qPCR was performed using LightCycler480 SYBR Green I Master (Roche Diagnostics, Indianapolis, IN, USA) at 94°C for 45 sec, followed by 40 cycles of 95°C for 30 sec, 60°C for 45 sec and 72°C for 30 sec, and then 4°C for 10 min. The primer sequences are listed in Table I. Samples were quantified using the 2−ΔΔCq method (18).

Table I.

Design of primer sequences.

Table I.

Design of primer sequences.

GeneForward primer sequenceReverse primer sequence
Runx2 5-CAGTTCCTAACGGGCACCAT-3 5-TTAGGGTCTCGGAGGGAAGG-3
Col I 5-TGACCTCAAGATGTGCCACT-3 5-GGGAGTTTCCATGAAGCCAC-3
OC 5-CATGAGAGCCCTCACA-3 5-AGAGCGACACCCTAGAC-3
β-actin 5-GCTCTCCAGAACATCACTCCTGCC-3 5-CGTTGTCATACCAGGAAATGAGCTT-3

[i] Runx2, runt-related transcription factor 2; Col I, type I collagen; OC, osteocalcin.

Enzyme-linked immunosorbent assay of alkaline phosphatase (ALP) and triglyceride (TG)

Following the treatment of BMSCs with genistein or GW9662, the activity of ALP and TG in cells was detected using an ALP and TG determination kit (Beyotime Institute of Biotechnology, Haimen, China) according to the manufacturers protocol. The optical density was read using a microplate reader (LabSystems Miltiskan MS Plate Reader; Thermo Fisher Scientific, Inc.) at 405 nm.

Western blotting for PPARγ

Following the application of genistein or GW9662 to BMSCs, equal quantities of protein were analyzed using a BCA protein assay kit (Beyotime Institute of Biotechnology), according to the manufacturers instructions. Protein was separated using 10% sodium dodecyl sulfate polyacrylamide (Sinopharm Chemical Reagent Co., Ltd.) gel electrophoresis (110 V; 45 min) and transferred to polyvinylidene difluoride membranes (EMD Millipore, Billerica, MA, USA). The membrane was blocked in 5% nonfat milk-PBS-Tween 20 solution (Shanghai Macklin Biochemical Co., Ltd.) for 1 h at room temperature, followed by separate incubation with polyclonal antibodies specific for PPAR (dilution, 1:1,000; goat anti-mouse; sc-1985; Santa Cruz Biotechnology, Inc., Dallas, TX, USA) and β-actin (dilution, 1:2,000; goat anti-mouse; sc-1616; Santa Cruz) at 4°C overnight. The membranes were incubated for 1 h at room temperature with horseradish peroxidase-conjugated secondary antibody (goat anti-mouse IgG; dilution, 1:5,000; sc-45101; Santa Cruz) in 5% nonfat milk-PBS-Tween 20. The membranes were visualized using enhanced chemiluminescence (Thermo Fisher Scientific, Inc.), and analyzed using a Gel-Doc 2000 imaging scanner (Bio-Rad Laboratories, Inc.).

Statistical analysis

All data are expressed as the mean ± standard error. Statistical analysis of data was performed using one-way analysis of variance and the statistical software package SPSS version 17.0 (SPSS, Inc., Chicago, IL, USA). P<0.05 was considered to indicate a statistically significant difference.

Results

Authenticating of BMSCs

The chemical structure of genistein is presented in Fig. 1. Fig. 2 demonstrates that the morphology of cultured BMSCs are spindle-shaped with serial subcultivation, homogeneity and multiplicity. The cell nucleus of stained BMSCs appeared dark blue (Fig. 2).

Effect of genistein on cell proliferation in BMSCs

Analysis indicated that genistein increased BMSC cell proliferation in a time- and dose-dependent manner (Fig. 3). When cells were treated with 20 µm genistein for 2 and 3 days, and 10 µm genistein for 3 days, BMSC cell proliferation was significantly increased compared with untreated BMSC cells (P<0.01; Fig. 3).

Effect of genistein on Runx2, Col I and OC mRNA expression in BMSCs

As presented in Fig. 4, the expression of Runx2, Col I and OC mRNA were significantly reduced following treatment with genistein. In BMSCs, the expression of Runx2 mRNA was significantly inhibited following treatment with 20 µm genistein for 2 days, the expression of Col I mRNA was significantly reduced following treatment with 5, 10 and 20 µm genistein for 2 days, and the expression of OC mRNA was significantly reduced following treatment with 10 and 20 µm genistein for 2 days (P<0.01; Fig. 4).

Effect of genistein on ALP and TG activity in BMSCs

Compared with BMSCs in the absence of genistein, the activity of ALP was significantly inhibited and the activity of TG was significantly enhanced following treatment with 20 µm genistein (P<0.01; Fig. 5).

Effect of genistein on PPARγ protein expression in BMSCs

To observe the mechanism of genistein on BMSCs, the protein expression of PPARγ was analyzed using western blotting. The results demonstrated that the protein expression of PPARγ was significantly increased following BMSC pretreatment with 20 µm genistein for 2 days (P<0.01; Fig. 6).

Effect of PPARγ downregulation on genistein-induced BMSC cell proliferation

GW9662 significantly inhibited PPARγ protein expression in BMSCs treated with 20 µm genistein for 2 days, compared with BMSCs treated only with 20 µm genistein (P<0.01; Fig. 7A and B). In addition, GW9662 significantly reduced the effect of 20 µm genistein on BMSC cell proliferation compared with cells treated only with 20 µm genistein (P<0.01; Fig. 7C).

Effect of PPARγ downregulation on Runx2, Col I and OC mRNA expression and the activity of ALP and TG in BMSCs

As presented in Fig. 8A, the effect of 20 µm genistein on the expression of Runx2, Col I and OC mRNAs was significantly reduced following pretreatment with a PPARγ inhibitor for 2 days (P<0.01), compared with cells treated only with 20 µm genistein for 2 days. In addition, the genistein-induced increase in TG activity and reduction in ALP activity were significantly inhibited by a PPARγ inhibitor (P<0.01; Fig. 8B and C).

Discussion

A number of local factors and hormones are required to transmit signals to transcription factors when BMSCs differentiate in osteogenesis, and these control the expression of specific genes during each stage of BMSC differentiation, thus controlling the osteoblast at each stage (1,2). Once mesenchymal stem cells become osteoblasts, the osteogenic cells proliferate as a result of mitotic growth factors, which ensure that a sufficient quantity of osteoblasts are generated for osteogenesis (19). Meanwhile, osteogenic cells undergo differentiation into mature osteoblasts during osteogenesis (20).

OC, ALP, Runx2 and Col I are derived during the synthesis of osteoblasts. At different stages of osteogenesis, only part of the aforementioned proteins and factors may be generated (21). With the generation of OC, Runx2 and Col I, osteoblasts will enter into different stages of differentiation (22). Thus, the synthesis and secretion of such proteins are significant markers of osteoblast differentiation, and affect the biological function and performance of osteoblasts (23).

In the present study, genistein significantly accelerated BMSC cell proliferation, reduced Runx2, Col I and OC mRNA expression, and inhibited the activity of ALP and increased the activity of TG, which suggests that genistein has the potential to be used as a BMSC inductive agent. In particular, Relic et al (24) reported that genistein induces adipogenesis through activating PPARγ pathway.

BMSCs possess a multipotent differentiation potential that allows them to differentiate into a variety of cell osteoblasts, including chondrocytes, adipocytes and myoblasts, by a number of induction pathways, and this directional differentiation can alter when the differentiation induction system changes (25). When osteogenesis- and chondrogenesis-inducing factors are present in BMSC culture systems, the expression of PPARγ is significantly increased and an increased number of adipocytes are generated (3). Osteoblasts are able to generate a variety of cytokines that regulate the differentiation and apoptosis of osteoclasts in various stages of differentiation proliferation, maturation and mineralization (26). Therefore, the effect of the PPARγ gene and its ligand on osteoblasts may alter the levels of cytokines in the bone marrow microenvironment, resulting in a direct or indirect influence on the differentiation and function of osteoclasts (3,8).

Results from the present study demonstrated that BMSC pretreatment with 20 µm genistein significantly activates PPARγ protein expression. Similarly, a previous report observed that genistein inhibits human osteosarcoma MG-63 cells by activating the PPARγ signaling pathway (27). In addition, Chatterjee et al (28) demonstrated that genistein prevents Alzheimers disease-associated inflammation through increasing PPARγ expression in cultured astrocytes (29).

PPAR was identified as a substance that may be activated by a peroxysome proliferation stimulator of a fatty acid-like compound (30). It was observed in vitro and in vivo that PPAR served an important role in the regulation of BMSC differentiation (31). A number of studies report that the PPARγ genes possesses an influence on the pathogenesis of osteoporosis induced by microgravity; under simulated microgravity conditions, the expression of PPARγ is increased, thus enhancing the activity of PPARγ, as well as its target gene adipsin and recombinant human leptin (32,33). The present study observed that downregulation of PPARγ reduced the effect of genistein-induced BMSC cell growth, inhibited genistein-induced adipogenic differentiation and suppressed the osteogenic potential of BMSCs.

In conclusion, the results from the current study demonstrate that genistein promotes cell growth, induces adipogenic differentiation and suppresses the osteogenic potential of BMSCs by upregulating PPARγ expression. To conclude, genistein may be a potential therapeutic agent for the treatment of orthopedic diseases.

Acknowledgements

The current study was supported by the National Natural Science Foundation of China subsidization project (no. 81301564), the Army Medical Science Youth Training Project (no. 13QNP184), the ‘Twelfth Five-Year Plan’ Science and Technology Research Project of Jilin Province Department of Education (no. 141) and the Jilin Province Science and Technology Department Project (no. 20130624003JC).

References

1 

Katsuda T, Tsuchiya R, Kosaka N, Yoshioka Y, Takagaki K, Oki K, Takeshita F, Sakai Y, Kuroda M and Ochiya T: Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Sci Rep. 3:11972013. View Article : Google Scholar : PubMed/NCBI

2 

Dumont N, Boyer L, Émond H, Celebi-Saltik B, Pasha R, Bazin R, Mantovani D, Roy DC and Pineault N: Medium conditioned with mesenchymal stromal cell-derived osteoblasts improves the expansion and engraftment properties of cord blood progenitors. Exp Hematol. 42:741–752.e1. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Kawai M, Green CB, Lecka-Czernik B, Douris N, Gilbert MR, Kojima S, Ackert-Bicknell C, Garg N, Horowitz MC, Adamo ML, et al: A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-gamma nuclear translocation. Proc Natl Acad Sci USA. 107:10508–10513. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Lv FH, Gao JZ, Teng QL and Zhang JY: Effect of folic acid and vitamin B12 on the expression of PPARγ, caspase-3 and caspase-8 mRNA in the abdominal aortas of rats with hyperlipidemia. Exp Ther Med. 6:184–188. 2013.PubMed/NCBI

5 

Zhou Y, Zhu ZL, Guan XX, Hou WW and Yu HY: Reciprocal roles between caffeine and estrogen on bone via differently regulating cAMP-PKA pathway: The possible mechanism for caffeine-induced osteoporosis in women and estrogens antagonistic effects. Med Hypotheses. 73:83–85. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Lu T, Huang Y, Wang H, Ma Y and Guan W: Multi-lineage potential research of bone marrow-derived stromal cells (BMSCs) from cattle. Appl Biochem Biotechnol. 172:21–35. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Fan J, Li J and Fan Q: Naringin promotes differentiation of bone marrow stem cells into osteoblasts by upregulating the expression levels of microRNA-20a and downregulating the expression levels of PPARgamma. Mol Med Rep. 12:4759–4765. 2015.PubMed/NCBI

8 

Weivoda MM and Hohl RJ: Geranylgeranyl pyrophosphate stimulates PPARγ expression and adipogenesis through the inhibition of osteoblast differentiation. Bone. 50:467–476. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Cao J, Ou G, Yang N, Ding K, Kream BE, Hamrick MW, Isales CM and Shi XM: Impact of targeted PPARγ disruption on bone remodeling. Mol Cell Endocrinol. 410:27–34. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Chen Y, Chen L, Yin Q, Gao H, Dong P, Zhang X and Kang J: Reciprocal interferences of TNF-α and Wnt1-β-catenin signaling axes shift bone marrow-derived stem cells towards osteoblast lineage after ethanol exposure. Cell Physiol Biochem. 32:755–765. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Hirayama K, Matsuzuka Y, Kamiya T, Ikeguchi M, Takagaki K and Itoh K: Metabolism of isoflavones found in the Pueraria thomsonii flower by human intestinal microbiota. Biosci Microflora. 30:135–140. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Kim SH, Kim CW, Jeon SY, Go RE, Hwang KA and Choi KC: Chemopreventive and chemotherapeutic effects of genistein, a soy isoflavone, upon cancer development and progression in preclinical animal models. Lab Anim Res. 30:143–150. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Nagaraju GP, Zafar SF and El-Rayes BF: Pleiotropic effects of genistein in metabolic, inflammatory, and malignant diseases. Nutr Rev. 71:562–572. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Menze ET, Esmat A, Tadros MG, Abdel-Naim AB and Khalifa AE: Genistein improves 3-NPA-induced memory impairment in ovariectomized rats: Impact of its antioxidant, anti-inflammatory and acetylcholinesterase modulatory properties. PLoS One. 10:e01172232015. View Article : Google Scholar : PubMed/NCBI

15 

Chen J, Duan Y, Zhang X, Ye Y, Ge B and Chen J: Genistein induces apoptosis by the inactivation of the IGF-1R-p-Akt signaling pathway in MCF-7 human breast cancer cells. Food Funct. 6:995–1000. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Liao MH, Tai YT, Cherng YG, Liu SH, Chang YA, Lin PI and Chen RM: Genistein induces oestrogen receptor-α gene expression in osteoblasts through the activation of mitogen-activated protein kinases-NF-κB-activator protein-1 and promotes cell mineralisation. Br J Nutr. 111:55–63. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Zeng X, Yu SP, Taylor T, Ogle M and Wei L: Protective effect of apelin on cultured rat bone marrow mesenchymal stem cells against apoptosis. Stem Cell Res (Amst). 8:357–367. 2012. View Article : Google Scholar

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Pauksch L, Hartmann S, Szalay G, Alt V and Lips KS: In vitro assessment of nanosilver-functionalized PMMA bone cement on primary human mesenchymal stem cells and osteoblasts. PLoS One. 9:e1147402014. View Article : Google Scholar : PubMed/NCBI

20 

Lee S, Cho HY, Bui HT and Kang D: The osteogenic or adipogenic lineage commitment of human mesenchymal stem cells is determined by protein kinase C delta. BMC Cell Biol. 15:422014. View Article : Google Scholar : PubMed/NCBI

21 

Antoniou J, Wang HT, Alaseem AM, Haglund L, Roughley PJ and Mwale F: The effect of Link N on differentiation of human bone marrow-derived mesenchymal stem cells. Arthritis Res Ther. 14:R2672012. View Article : Google Scholar : PubMed/NCBI

22 

Nichols RA Jr, Niagro FD, Borke JL and Cuenin MF: Mechanical stretching of mouse calvarial osteoblasts in vitro models changes in MMP-2 and MMP-9 expression at the bone-implant interface. J Oral Implantol. May 11–2015.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

23 

Hu HM, Yang L, Wang Z, Liu YW, Fan JZ, Fan J, Liu J and Luo ZJ: Overexpression of integrin α2 promotes osteogenic differentiation of hBMSCs from senile osteoporosis through the ERK pathway. Int J Clin Exp Pathol. 6:841–852. 2013.PubMed/NCBI

24 

Relic B, Zeddou M, Desoroux A, Beguin Y, de Seny D and Malaise MG: Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts. Lab Invest. 89:811–822. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Arrigoni C, De Luca P, Gilardi M, Previdi S, Broggini M and Moretti M: Direct but not indirect co-culture with osteogenically differentiated human bone marrow stromal cells increases RANKL-OPG ratio in human breast cancer cells generating bone metastases. Mol Cancer. 13:2382014. View Article : Google Scholar : PubMed/NCBI

26 

Choudhary S, Goetjen A, Estus T, Jacome-Galarza CE, Aguila HL, Lorenzo J and Pilbeam C: Serum amyloid A3 secreted by preosteoclasts inhibits parathyroid hormone-stimulated cAMP signaling in murine osteoblasts. J Biol Chem. 23–Dec;2015.(Epub ahead of print). pii jbc. M115.686576. PubMed/NCBI

27 

Song M, Tian X, Lu M, Zhang X, Ma K, Lv Z, Wang Z, Hu Y, Xun C, Zhang Z and Wang S: Genistein exerts growth inhibition on human osteosarcoma MG-63 cells via PPARγ pathway. Int J Oncol. 46:1131–1140. 2015.PubMed/NCBI

28 

Chatterjee G, Roy D, Khemka VK, Chattopadhyay M and Chakrabarti S: Genistein, the isoflavone in soybean, causes amyloid beta peptide accumulation in human neuroblastoma cell line: Implications in Alzheimers disease. Aging Dis. 6:456–465. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Valles SL, Dolz-Gaiton P, Gambini J, Borras C, Lloret A, Pallardo FV and Viña J: Estradiol or genistein prevent Alzheimers disease-associated inflammation correlating with an increase PPAR gamma expression in cultured astrocytes. Brain Res. 1312:138–144. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Zhuang H, Zhang X, Zhu C, Tang X, Yu F, Shang GW and Cai X: Molecular mechanisms of PPARγ governing MSC osteogenic and adipogenic differentiation. Curr Stem Cell Res Ther. 31–May;2015.(Epub ahead of print).

31 

Zhou H, Yang X, Wang N, Zhang Y and Cai G: Tigogenin inhibits adipocytic differentiation and induces osteoblastic differentiation in mouse bone marrow stromal cells. Mol Cell Endocrinol. 270:17–22. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Wang L, Li L, Gao H and Li Y: Effect of pioglitazone on transdifferentiation of preosteoblasts from rat bone mesenchymal stem cells into adipocytes. J Huazhong Univ Sci Technolog Med Sci. 32:530–533. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Lee NJ, Doyle KL, Sainsbury A, Enriquez RF, Hort YJ, Riepler SJ, Baldock PA and Herzog H: Critical role for Y1 receptors in mesenchymal progenitor cell differentiation and osteoblast activity. J Bone Miner Res. 25:1736–1747. 2010. View Article : Google Scholar : PubMed/NCBI

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May-2016
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Zhang LY, Xue HG, Chen JY, Chai W and Ni M: Genistein induces adipogenic differentiation in human bone marrow mesenchymal stem cells and suppresses their osteogenic potential by upregulating PPARγ. Exp Ther Med 11: 1853-1858, 2016
APA
Zhang, L., Xue, H., Chen, J., Chai, W., & Ni, M. (2016). Genistein induces adipogenic differentiation in human bone marrow mesenchymal stem cells and suppresses their osteogenic potential by upregulating PPARγ. Experimental and Therapeutic Medicine, 11, 1853-1858. https://doi.org/10.3892/etm.2016.3120
MLA
Zhang, L., Xue, H., Chen, J., Chai, W., Ni, M."Genistein induces adipogenic differentiation in human bone marrow mesenchymal stem cells and suppresses their osteogenic potential by upregulating PPARγ". Experimental and Therapeutic Medicine 11.5 (2016): 1853-1858.
Chicago
Zhang, L., Xue, H., Chen, J., Chai, W., Ni, M."Genistein induces adipogenic differentiation in human bone marrow mesenchymal stem cells and suppresses their osteogenic potential by upregulating PPARγ". Experimental and Therapeutic Medicine 11, no. 5 (2016): 1853-1858. https://doi.org/10.3892/etm.2016.3120