Abstract
Human placenta-derived mesenchymal stem cells (hPDMSCs) can differentiate into different types of cells and thus have tremendous potential for cell therapy and tissue engineering. LIM mineralization protein-1 (LMP-1) plays an important role in osteoblast differentiation, maturation and bone formation. To determine a global effect of LMP-1 on hPDMSCs, we designed a study using a proteomic approach combined with adenovirus-mediated gene transfer of LMP-1 to identify LMP-1-induced changes in hPDMSCs on proteome level. We have generated proteome maps of undifferentiated hPDMSCs and LMP-1 induced hPDMSCs. Two dimensional gel electrophoresis revealed 22 spots with at least 2.0-fold changes in expression and 15 differently expressed proteins were successfully identified by MALDI-TOF-MS. The proteins regulated by LMP-1 included cytoskeletal proteins, cadmium-binding proteins, and metabolic proteins, etc. The expression of some identified proteins was confirmed by further Western blot analyses. Our results will play an important role in better elucidating the underlying molecular mechanism in LMP-1 included hPDMSCs differentiation into osteoblasts.
Similar content being viewed by others
References
Alvarez-Silva M, Belo-Diabangouaya P, Salaun J, Dieterlen-Lievre F (2003) Mouse placenta is a major hematopoietic organ. Development 130:5437–5444
Annunen-Rasila J, Ohlmeier S, Tuokko H, Veijola J, Majamaa K (2007) Proteome and cytoskeleton responses in osteosarcoma cells with reduced OXPHOS activity. Proteomics 7:2189–2200
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet 25:25–29
Boden SD, Liu Y, Hair GA, Helms JA, Hu D, Racine M, Nanes MS, Titus L (1998) LMP-1, a LIM-domain protein, mediates BMP-6 effects on bone formation. Endocrinology 139:5125–5134
Bunger MH, Langdahl BL, Andersen T, Husted L, Lind M, Eriksen EF, Bunger CE (2003) Semiquantitative mRNA measurements of osteoinductive growth factors in human iliac-crest bone: expression of LMP splice variants in human bone. Calcif Tissue Int 73:446–454
Chien CC, Yen BL, Lee FK, Lai TH, Chen YC, Chan SH, Huang HI (2006) In vitro differentiation of human placenta-derived multipotent cells into hepatocyte-like cells. Stem Cells 24:1759–1768
Conget PA, Minguell JJ (2000) Adenoviral-mediated gene transfer into ex vivo expanded human bone marrow mesenchymal progenitor cells. Exp Hematol 28:382–390
Cooper JA, Schafer DA (2000) Control of actin assembly and disassembly at filament ends. Curr Opin Cell Biol 12:97–103
Dirim A, Haberal AN, Goren MR, Tekin MI, Peskircioglu L, Demirhan B, Ozkardes H (2008) VEGF, COX-2, and PCNA expression in renal cell carcinoma subtypes and their prognostic value. Int Urol Nephrol 40:861–868
Dyballa N, Metzger S (2009) Fast and sensitive colloidal coomassie G-250 staining for proteins in polyacrylamide gels. J Vis Exp 30:1431
Faca VM (2012) Human mesenchymal stromal cell proteomics: contribution for identification of new markers and targets for medicine intervention. Expert Rev Proteomics 9:217–230
Fei Q, Boden SD, Sangadala S, Viggeswarapu M, Liu Y, Titus L (2007) Truncated human LMP-1 triggers differentiation of C2C12 cells to an osteoblastic phenotype in vitro. Acta Biochim Biophys Sin (Shanghai) 39:693–700
Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K (2004) Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem Cells 22:649–658
Gillette JM, Nielsen-Preiss SM (2004) The role of annexin 2 in osteoblastic mineralization. J Cell Sci 117:441–449
Guido RV, Oliva G (2009) Structure-based drug discovery for tropical diseases. Curr Top Med Chem 9:824–843
Halvorsen YD, Franklin D, Bond AL, Hitt DC, Auchter C, Boskey AL, Paschalis EP, Wilkison WO, Gimble JM (2001) Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. Tissue Eng 7:729–741
Huang HI (2007) Isolation of human placenta-derived multipotent cells and in vitro differentiation into hepatocyte-like cells. Curr Protoc Stem Cell Biol Chap. 1, Unit 1E 1
Hughes CS, Nuhn AA, Postovit LM, Lajoie GA (2011a) Proteomics of human embryonic stem cells. Proteomics 11:675–690
Hughes CS, Radan L, Betts D, Postovit LM, Lajoie GA (2011b) Proteomic analysis of extracellular matrices used in stem cell culture. Proteomics 11:3983–3991
Kelleher MT, Fruhwirth G, Patel G, Ofo E, Festy F, Barber PR, Ameer-Beg SM, Vojnovic B, Gillett C, Coolen A, Keri G, Ellis PA, Ng T (2009) The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients. Target Oncol 4:235–252
Kim HS, Viggeswarapu M, Boden SD, Liu Y, Hair GA, Louis-Ugbo J, Murakami H, Minamide A, Suh DY, Titus L (2003) Overcoming the immune response to permit ex vivo gene therapy for spine fusion with human type 5 adenoviral delivery of the LIM mineralization protein-1 cDNA. Spine 28:219–226
Kim SH, Jun S, Jang HS, Lim SK (2005) Identification of parathyroid hormone-regulated proteins in mouse bone marrow cells by proteomics. Biochem Biophys Res Commun 330:423–429
Kirsch T, Nah HD, Shapiro IM, Pacifici M (1997) Regulated production of mineralization-competent matrix vesicles in hypertrophic chondrocytes. J Cell Biol 137:1149–1160
Kitching R, Qi S, Li V, Raouf A, Vary CP, Seth A (2002) Coordinate gene expression patterns during osteoblast maturation and retinoic acid treatment of MC3T3-E1 cells. J Bone Miner Metab 20:269–280
Kurpinski K, Chu J, Wang D, Li S (2009) Proteomic profiling of mesenchymal stem cell responses to mechanical strain and TGF-β1. Cell Mol Bioeng 2:606–614
Lee SK, Kim Y, Kim SS, Lee JH, Cho K, Lee SS, Lee ZW, Kwon KH, Kim YH, Suh-Kim H, Yoo JS, Park YM (2009) Differential expression of cell surface proteins in human bone marrow mesenchymal stem cells cultured with or without basic fibroblast growth factor containing medium. Proteomics 9:4389–4405
Liang P, MacRae TH (1997) Molecular chaperones and the cytoskeleton. J Cell Sci 110:1431–1440
Margaritescu C, Raica M, Simionescu C, Mogoanta L, Surpateanu M, Jaubert F, Bogdan F (2005) Tumoral stroma of salivary pleomorphic adenoma—histopathological, histochemical and immunohistochemical study. Rom J Morphol Embryol 46:211–223
Mathews MB, Bernstein RM, Franza BR Jr, Garrels JI (1984) Identity of the proliferating cell nuclear antigen and cyclin. Nature 309:374–376
Matikainen T, Laine J (2005) Placenta—an alternative source of stem cells. Toxicol Appl Pharmacol 207:544–549
Miao Z, Jin J, Chen L, Zhu J, Huang W, Zhao J, Qian H, Zhang X (2006) Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biol Int 30:681–687
Minamide A, Boden SD, Viggeswarapu M, Hair GA, Oliver C, Titus L (2003) Mechanism of bone formation with gene transfer of the cDNA encoding for the intracellular protein LMP-1. J Bone Joint Surg Am 85-A:1030–1039
Moldovan GL, Pfander B, Jentsch S (2007) PCNA, the maestro of the replication fork. Cell 129:665–679
Morsczeck C, Moehl C, Gotz W, Heredia A, Schaffer TE, Eckstein N, Sippel C, Hoffmann KH (2005) In vitro differentiation of human dental follicle cells with dexamethasone and insulin. Cell Biol Int 29:567–575
Nelson KJ, Knutson ST, Soito L, Klomsiri C, Poole LB, Fetrow JS (2011) Analysis of the peroxiredoxin family: using active-site structure and sequence information for global classification and residue analysis. Proteins 79:947–964
Nygard O, Nilsson L (1990) Kinetic determination of the effects of ADP-ribosylation on the interaction of eukaryotic elongation factor 2 with ribosomes. J Biol Chem 265:6030–6034
Panepucci RA, Siufi JL, Silva WA Jr, Proto-Siquiera R, Neder L, Orellana M, Rocha V, Covas DT, Zago MA (2004) Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells. Stem Cells 22:1263–1278
Park HW, Shin JS, Kim CW (2007) Proteome of mesenchymal stem cells. Proteomics 7:2881–2894
Parolini O, Alviano F, Bagnara GP, Bilic G, Buhring HJ, Evangelista M, Hennerbichler S, Liu B, Magatti M, Mao N, Miki T, Marongiu F, Nakajima H, Nikaido T, Portmann-Lanz CB, Sankar V, Soncini M, Stadler G, Surbek D, Takahashi TA, Redl H, Sakuragawa N, Wolbank S, Zeisberger S, Zisch A, Strom SC (2008) Concise review: isolation and characterization of cells from human term placenta: outcome of the first international workshop on placenta derived stem cells. Stem Cells 26:300–311
Portmann-Lanz CB, Schoeberlein A, Portmann R, Mohr S, Rollini P, Sager R, Surbek DV (2010) Turning placenta into brain: placental mesenchymal stem cells differentiate into neurons and oligodendrocytes. Am J Obstet Gynecol 202:294.e1–294.e11
Prelich G, Tan CK, Kostura M, Mathews MB, So AG, Downey KM, Stillman B (1987) Functional identity of proliferating cell nuclear antigen and a DNA polymerase-delta auxiliary protein. Nature 326:517–520
Rhee SG, Kang SW, Chang TS, Jeong W, Kim K (2001) Peroxiredoxin, a novel family of peroxidases. IUBMB Life 52:35–41
Ryazanov AG, Rudkin BB, Spirin AS (1991) Regulation of protein synthesis at the elongation stage. New insights into the control of gene expression in eukaryotes. FEBS Lett 285:170–175
Stenderup K, Justesen J, Clausen C, Kassem M (2003) Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33:919–926
Strakova Z, Livak M, Krezalek M, Ihnatovych I (2008) Multipotent properties of myofibroblast cells derived from human placenta. Cell Tissue Res 332:479–488
Strohbach CA, Rundle CH, Wergedal JE, Chen ST, Linkhart TA, Lau KH, Strong DD (2008) LMP-1 retroviral gene therapy influences osteoblast differentiation and fracture repair: a preliminary study. Calcif Tissue Int 83:202–211
Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354
van Hoof D, Krijgsveld J, Mummery C (2012) Proteomic analysis of stem cell differentiation and early development. Cold Spring Harb Perspect Biol 4:500-501
Walker CA, Spinale FG (1999) The structure and function of the cardiac myocyte: a review of fundamental concepts. J Thorac Cardiovasc Surg 118:375–382
Wang W, Kirsch T (2002) Retinoic acid stimulates annexin-mediated growth plate chondrocyte mineralization. J Cell Biol 157:1061–1069
Wang X, Cui F, Madhu V, Dighe AS, Balian G, Cui Q (2011) Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation. Growth Factors 29:36–48
Wei B, Yuan S, Gao Y, Bing L (2008) Hematopoietic potential of mouse placenta with the application of placenta flushing. Biol Res 41:261–270
William F, Mroczkowski B, Cohen S, Kraft AS (1988) Differentiation of HL-60 cells is associated with an increase in the 35-kDa protein lipocortin I. J Cell Physiol 137:402–410
Ye NS, Chen J, Luo GA, Zhang RL, Zhao YF, Wang YM (2006) Proteomic profiling of rat bone marrow mesenchymal stem cells induced by 5-azacytidine. Stem Cells Dev 15:665–676
Yen BL, Huang HI, Chien CC, Jui HY, Ko BS, Yao M, Shun CT, Yen ML, Lee MC, Chen YC (2005) Isolation of multipotent cells from human term placenta. Stem Cells 23:3–9
Yi B, Zeng J, Wang G, Qian G, Lu K (2013) Annexin A1 protein regulates the expression of PMVEC cytoskeletal proteins in CBDL rat serum-induced pulmonary microvascular remodeling. J Transl Med 11:98
Yoon ST, Boden SD (2002) Osteoinductive molecules in orthopaedics: basic science and preclinical studies. Clin Orthop Relat Res 395:33–43
Yoon ST, Park JS, Kim KS, Li J, Attallah-Wasif ES, Hutton WC, Boden SD (2004) ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of proteoglycans and BMPs in vitro and in vivo. Spine 29:2603–2611
Zhang Y, Li CD, Jiang XX, Li HL, Tang PH, Mao N (2004) Comparison of mesenchymal stem cells from human placenta and bone marrow. Chin Med J (Engl) 117:882–887
Zhang X, Mitsuru A, Igura K, Takahashi K, Ichinose S, Yamaguchi S, Takahashi TA (2006) Mesenchymal progenitor cells derived from chorionic villi of human placenta for cartilage tissue engineering. Biochem Biophys Res Commun 340:944–952
Zhang AX, Yu WH, Ma BF, Yu XB, Mao FF, Liu W, Zhang JQ, Zhang XM, Li SN, Li MT, Lahn BT, Xiang AP (2007) Proteomic identification of differently expressed proteins responsible for osteoblast differentiation from human mesenchymal stem cells. Mol Cell Biochem 304:167–179
Acknowledgments
This work was supported by the 10th Science and Technology Supporting Program project from Zhenjiang city (SH2010043) and Natural Science Foundation of Jilin Province (20130101017jc).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhu, Z., Liu, Z., Liu, J. et al. Proteomic profiling of human placenta-derived mesenchymal stem cells upon transforming LIM mineralization protein-1 stimulation. Cytotechnology 67, 285–297 (2015). https://doi.org/10.1007/s10616-013-9684-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10616-013-9684-x