Original Articles

The Study of LPL Gene Expression during Differentiation of Human BM-MSC into Adipocytes

Abstract

Background: Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Recent evidence shows that LPL plays important roles in inflammation and obesity, implies that it is an appropriate general target for chemo preventive and chemotherapeutic agents. Thus, we reported LPL expression before and after BM-MSCs differentiation into adipocytes.Methods: In this study, we isolated mesenchymal stem cells from human bone marrow by Ficoll - gradient and then their surface markers by flow cytometry confirmed and osteoblastic and adipocytes differentiation by Dexamethasone protocol were done and confirmed by staining .Then qualitative expression of LPL gene by RT-PCR before and after of differentiation into adipocytes .Statistical analysis was performed by paired t test and by using Pfaffl and graph pad software.Results: After 14 days, analysis of morphology with invert microscopy indicated that BM-MSCs have ability of differentiation capacities into adipocytes. Investigations of expression of LPL showed BM-MSC that served as negative control have not expression of LPL while in BM-MSCs derived- adipocyte have found significant expression of LPL.Conclusions: BM-MSCs can differentiate into either adipocytes or osteoblastic cells that in decision between the two lineages, LPL has the important role through activation inhibiting osteoblastic in favor of adipogenic differentiation. LPL could be an effective agent on tumor suppressing with catalyzes the hydrolysis of plasma TG.  LPL gene deficiency, such as due to chromosome 8p22 loss, LPL gene polymorphism, and epigenetic changes increases cancer risk, especially in the prostate.

Kim DS, Lee MW, Yoo KH, Lee TH, Kim HJ, Jang IK, et al. Gene expression profiles of human adipose tissue-derived mesenchymal stem cells are modified by cell culture density. PloS one. 2014;9(1):e83363.

Neuss S, Becher E, Woltje M, Tietze L, Jahnen-Dechent W. Func- tional expression of HGF and HGF receptor/c-met in adult human mes- enchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing. Stem cells (Dayton, Ohio). 2004;22(3):405-14.

Deans RJ, Moseley AB. Mesenchymalstem cells: biology and poten- tial clinical uses. Experimental hematology. 2000;28(8):875-84.

De Ugarte DA, Alfonso Z, Zuk PA, Elbarbary A, Zhu M, Ashjian P, et al. Differential expression of stem cell mobilization-associated mol- ecules on multi-lineagecells from adipose tissue and bone marrow. Im- munology letters. 2003;89(2-3):267-70.

Penkov DN, Egorov AD, Mozgovaya MN, Tkachuk VA. Insulin re- sistance and adipogenesis: role of transcription and secreted factors. Biochemistry Biokhimiia. 2013;78(1):8-18.

Shi L, Yang X. [Differentiation potential and application of stem cells from adipose tissue]. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery. 2012;26(8):1007-11.

Ling H, Li X, Yao CH, Hu B, Liao D, Feng S, et al. The physiological and pathophysiological roles of adipocyte miRNAs. Biochemistry and cell biology = Biochimie et biologie cellulaire. 2013;91(4):195-202.

Modica S, Wolfrum C. Bone morphogenic proteins signaling in adipogenesis and energy homeostasis. Biochimica et biophysica acta. 2013;1831(5):915-23.

Sarjeant K, Stephens JM. Adipogenesis. Cold Spring Harbor perspec- tives in biology. 2012;4(9):a008417.

Lehrke M, Lazar MA. The many faces of PPARgamma. Cell. 2005;123(6):993-9.

Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARgamma. Annual review of biochemistry. 2008;77:289-312.

Perera RJ, Marcusson EG, Koo S, Kang X, Kim Y, White N, et al. Identification of novel PPARgamma target genes in primary human adipocytes. Gene. 2006;369:90-9.

Nakachi Y, Yagi K, Nikaido I, Bono H, Tonouchi M, Schonbach C, et al. Identification of novel PPARgamma target genes by integrated analysis of ChIP-on-chip and microarray expression data during adipo- cyte differentiation. Biochemical and biophysical research communica- tions. 2008;372(2):362-6.

Kang S, Bennett CN, Gerin I, Rapp LA, Hankenson KD, Macdou- gald OA. Wnt signaling stimulates osteoblastogenesis of mesenchymal precursors by suppressing CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma. The Journal of bio- logical chemistry. 2007;282(19):14515-24.

Astapova O, Leff T. Adiponectin and PPARgamma: cooperative and interdependent actions of two key regulators of metabolism. Vitamins and hormones. 2012;90:143-62.

Sekiya I, Larson BL, Vuoristo JT, Cui JG, Prockop DJ. Adipogenic differentiation of human adult stem cells from bone marrow stroma (MSCs). Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2004;19(2):256- 64.

Lecka-Czernik B, Gubrij I, Moerman EJ, Kajkenova O, Lipschitz DA, Manolagas SC, et al. Inhibition of Osf2/Cbfa1 expression and ter- minal osteoblast differentiation by PPARgamma2. Journal of cellular biochemistry. 1999;74(3):357-71.

Ghosh-Choudhury N, Windle JJ, Koop BA, Harris MA, Guer- rero DL, Wozney JM, et al. Immortalized murine osteoblasts derived from BMP 2-T-antigen expressing transgenic mice. Endocrinology. 1996;137(1):331-9.

Thompson DL, Lum KD, Nygaard SC, Kuestner RE, Kelly KA, Gimble JM, et al. The derivation and characterization of stromal cell lines from the bone marrow of p53-/- mice: new insights into osteoblast and adipocyte differentiation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 1998;13(2):195-204.

Cicione C, Muinos-Lopez E, Hermida-Gomez T, Fuentes-Boquete I, Diaz-Prado S, Blanco FJ. Effects of severe hypoxia on bone marrow mesenchymal stem cells differentiation potential. Stem cells interna- tional. 2013;2013:232896.

Rosen ED, Hsu C-H, Wang X, Sakai S, Freeman MW, Gonzalez FJ, et al. C/EBPα induces adipogenesis through PPARγ: a unified pathway. Genes & development. 2002;16(1):22-6.

Takada I. [Switching of osteoblastogenesis versus adipogenesis]. Clinical calcium. 2012;22(5):629-36.

Cao JJ. Effects of obesity on bone metabolism. Journal of orthopae- dic surgery and research. 2011;6:30.

Rozman C, Feliu E, Berga L, Reverter JC, Climent C, Ferran MJ. Age-related variations of fat tissue fraction in normal human bone mar- row depend both on size and number of adipocytes: a stereological study. Experimental hematology. 1989;17(1):34-7.

BaeKH, Kim WK, Lee SC. Involvement of protein tyrosine phos- phatases in adipogenesis: new anti-obesity targets? BMB reports. 2012;45(12):700-6.

Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. The New England journal of medicine.1997;336(19):1365-72.

Juneja HS, Gardner FH. Functionally abnormal marrow stromal cells in aplastic anemia. Experimental hematology. 1985;13(3):194-9.

Chen Q, Yuan Y, Chen T. Morphology, differentiation and adhesion molecule expression changes ofbone marrow mesenchymal stem cells from acute myeloid leukemia patients. Molecular medicine reports. 2014;9(1):293-8.

Zhao J, Yi C, Zheng Y, Li L, Qiu X, Xia W, et al. Enhancement of fat graft survival by bone marrow-derived mesenchymal stem cell therapy. Plastic and reconstructive surgery. 2013;132(5):1149-57.

Files
IssueVol 6 No 1 (2014) QRcode
SectionOriginal Articles
Keywords
Mesenchymal stem cell Differentiation Adipocyte Lipoprotein lipase

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Razavi babaheidari S R, Mousavi Hosseini K, Atashi A, Oodi A, Esmaeili S. The Study of LPL Gene Expression during Differentiation of Human BM-MSC into Adipocytes. Basic Clin Cancer Res. 2014;6(1):16-21.