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Comprehensive transcriptome analysis of mesenchymal stem cells in elderly patients with osteoporosis

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Abstract

Objective

To explore the role of aging in the pathogenesis of osteoporosis, several differentially expressed genes (DEGs) and altered biological pathways were identified in mesenchymal stem cells (MSCs) in elderly patients with osteoporosis.

Methods

Raw data were downloaded from Gene Expression Omnibus database. A total of 14 human MSC samples were available, including five samples from elderly patients suffering from osteoporosis, five controls from young non-osteoporotic donors and five controls from old non-osteoporotic donors. The DEGs were identified using LIMMA package among the three groups. Gene ontology and KEGG pathway analysis were carried out using DAVID. A protein–protein interaction (PPI) network of DEGs was constructed with STRING and then visualized with Cytoscape.

Results

A total of 3179 DEGs were screened, including 1071 up- and 2108 down-regulated genes. Compared with young and old controls, 271 and 781 genes were up-regulated in osteoporosis, respectively, and 17 genes were shared. Function and pathway enrichment showed that the up-regulated genes in osteoporosis were involved in extracellular matrix (ECM)–receptor interaction, focal adhesion and mammalian target of rapamycin signaling pathway. Moreover, a range of genes linked to cell adhesion, ECM–receptor interaction and cell cycle were revealed in the PPI network, such as transforming growth factor beta 1, insulin-like growth factor 2 and integrin beta 2.

Conclusion

A number of DEGs and altered pathways were screened in osteoporosis. Our study provided insights into the role of aging in the pathogenesis of osteoporosis and some DEGs might be potential biomarkers for osteoporosis.

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References

  1. Mithal A, Kaur P (2012) Osteoporosis in Asia: a call to action. Curr Osteoporos Rep 10(4):245–247

    Article  PubMed  Google Scholar 

  2. Qu B, Ma Y, Yan M, Wu H-H, Fan L, Liao D-F, Pan X-M, Hong Z (2014) The economic burden of fracture patients with osteoporosis in western China. Osteoporos Int:1–8

  3. Raisz LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115(12):3318–3325

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD (1996) Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 11(3):337–349

    Article  CAS  PubMed  Google Scholar 

  5. Pacifici R (2008) Estrogen deficiency, T cells and bone loss. Cell Immunol 252(1–2):68–80

    Article  CAS  PubMed  Google Scholar 

  6. Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377(9773):1276–1287

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. D’Amelio P, Grimaldi A, Di Bella S, Brianza SZ, Cristofaro MA, Tamone C, Giribaldi G, Ulliers D, Pescarmona GP, Isaia G (2008) Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone 43(1):92–100

    Article  PubMed  Google Scholar 

  8. Binder NB, Niederreiter B, Hoffmann O, Stange R, Pap T, Stulnig TM, Mack M, Erben RG, Smolen JS, Redlich K (2009) Estrogen-dependent and CC chemokine receptor-2–dependent pathways determine osteoclast behavior in osteoporosis. Nat Med 15(4):417–424

    Article  CAS  PubMed  Google Scholar 

  9. Horstman AM, Dillon EL, Urban RJ, Sheffield-Moore M (2012) The role of androgens and estrogens on healthy aging and longevity. J Gerontol A Biol Sci Med Sci 67:1140–1152

    Article  PubMed Central  PubMed  Google Scholar 

  10. Bayne S, Li H, Jones ME, Pinto AR, Van Sinderen M, Drummond A, Simpson ER, Liu J-P (2011) Estrogen deficiency reversibly induces telomere shortening in mouse granulosa cells and ovarian aging in vivo. Protein Cell 2(4):333–346

    Article  CAS  PubMed  Google Scholar 

  11. Das S, Crockett JC (2013) Osteoporosis—a current view of pharmacological prevention and treatment. Drug Des Devel Ther 7:435

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Negredo E, Domingo P, Ferrer E, Estrada V, Curran A, Navarro A, Isernia V, Rosales J, Pérez-Álvarez N, Puig J (2014) Peak bone mass in young HIV-infected patients compared with healthy controls. JAIDS 65(2):207–212

    PubMed  Google Scholar 

  13. Altindag O, Erel O, Soran N, Celik H, Selek S (2008) Total oxidative/anti-oxidative status and relation to bone mineral density in osteoporosis. Rheumatol Int 28(4):317–321

    Article  CAS  PubMed  Google Scholar 

  14. Sánchez-Rodríguez MA, Ruiz-Ramos M, Correa-Muñoz E, Mendoza-Núñez VM (2007) Oxidative stress as a risk factor for osteoporosis in elderly Mexicans as characterized by antioxidant enzymes. BMC Musculoskelet Disord 8(1):124

    Article  PubMed Central  PubMed  Google Scholar 

  15. Duque G (2008) Bone and fat connection in aging bone. Curr Opin Rheumatol 20(4):429–434. doi:10.1097/BOR.0b013e3283025e9c (00002281-200807000-00010 [pii])

    Article  CAS  PubMed  Google Scholar 

  16. Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21(2):195–214

    Article  CAS  PubMed  Google Scholar 

  17. Manolagas SC (2010) From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 31(3):266–300

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Rinker TE, Hammoudi TM, Kemp ML, Lu H, Temenoff JS (2014) Interactions between mesenchymal stem cells, adipocytes, and osteoblasts in a 3D tri-culture model of hyperglycemic conditions in the bone marrow microenvironment. Integr Biol 6(3):324–337

    Article  CAS  Google Scholar 

  19. Haasters F, Docheva D, Gassner C, Popov C, Böcker W, Mutschler W, Schieker M, Prall WC (2014) Mesenchymal stem cells from osteoporotic patients reveal reduced migration and invasion upon stimulation with BMP-2 or BMP-7. Biochem Biophys Res Commun 452(1):118–123

    Article  CAS  PubMed  Google Scholar 

  20. Benisch P, Schilling T, Klein-Hitpass L, Frey SP, Seefried L, Raaijmakers N, Krug M, Regensburger M, Zeck S, Schinke T (2012) The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors. PLoS One 7(9):e45142

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315

    Article  CAS  PubMed  Google Scholar 

  22. Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. doi:10.2202/1544-6115.1027

    PubMed  Google Scholar 

  23. Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4(5):P3

    Article  PubMed  Google Scholar 

  24. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C, Jensen LJ (2013) STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41(Database issue):D808–D815. doi:10.1093/nar/gks1094

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Kohl M, Wiese S, Warscheid B (2011) Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol 696:291–303. doi:10.1007/978-1-60761-987-1_18

    Article  CAS  PubMed  Google Scholar 

  26. Silver JJ, Einhorn TA (1995) Osteoporosis and aging: current update. Clin Orthop Relat Res 316:10–20

    PubMed  Google Scholar 

  27. Chen XD, Dusevich V, Feng JQ, Manolagas SC, Jilka RL (2007) extracellular matrix made by bone marrow cells facilitates expansion of marrow-derived mesenchymal progenitor cells and prevents their differentiation into osteoblasts. J Bone Miner Res 22(12):1943–1956

    Article  CAS  PubMed  Google Scholar 

  28. Bi Y, Stuelten CH, Kilts T, Wadhwa S, Iozzo RV, Robey PG, Chen X-D, Young MF (2005) Extracellular matrix proteoglycans control the fate of bone marrow stromal cells. J Biol Chem 280(34):30481–30489

    Article  CAS  PubMed  Google Scholar 

  29. Rappaport N, Nativ N, Stelzer G, Twik M, Guan-Golan Y, Stein TI, Bahir I, Belinky F, Morrey CP, Safran M, Lancet D (2013) MalaCards: an integrated compendium for diseases and their annotation. Database. doi:10.1093/database/bat018

    PubMed Central  PubMed  Google Scholar 

  30. Burridge K, Chrzanowska-Wodnicka M (1996) Focal adhesions, contractility, and signaling. Annu Rev Cell Dev Biol 12(1):463–519

    Article  CAS  PubMed  Google Scholar 

  31. Salasznyk RM, Klees RF, Williams WA, Boskey A, Plopper GE (2007) Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells. Exp Cell Res 313(1):22–37. doi:10.1016/j.yexcr.2006.09.013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Young SR, Gerard-O’Riley R, Kim JB, Pavalko FM (2009) Focal adhesion kinase is important for fluid shear stress-induced mechanotransduction in osteoblasts. J Bone Miner Res 24(3):411–424

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Glantschnig H, Fisher JE, Wesolowski G, Rodan GA, Reszka AA (2003) M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell Death Differ 10(10):1165–1177. doi:10.1038/sj.cdd.4401285

    Article  CAS  PubMed  Google Scholar 

  34. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342. doi:10.1038/nature01658

    Article  CAS  PubMed  Google Scholar 

  35. Xian L, Wu X, Pang L, Lou M, Rosen CJ, Qiu T, Crane J, Frassica F, Zhang L, Rodriguez JP (2012) Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat Med 18(7):1095–1101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Liu Y, Berendsen AD, Jia S, Lotinun S, Baron R, Ferrara N, Olsen BR (2012) Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation. J Clin Investig 122(9):3101–3113. doi:10.1172/JCI61209

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Olayioye MA, Badache A, Daly JM, Hynes NE (2001) An essential role for Src kinase in ErbB receptor signaling through the MAPK pathway. Exp Cell Res 267(1):81–87. doi:10.1006/excr.2001.5242

    Article  CAS  PubMed  Google Scholar 

  38. Park BL, Han IK, Lee HS, Kim LH, Kim SJ, Shin HD (2003) Identification of novel variants in transforming growth factor-beta 1 (TGFB1) gene and association analysis with bone mineral density. Hum Mutat 22(3):257–258

    Article  Google Scholar 

  39. Langdahl BL, Uitterlinden AG, Ralston SH, Trikalinos TA, Balcells S, Brandi ML, Scollen S, Lips P, Lorenc R, Obermayer-Pietsch B (2008) Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: the GENOMOS study. Bone 42(5):969–981

    Article  CAS  PubMed  Google Scholar 

  40. Hamet P, Tremblay J (2003) Genes of aging. Metabolism 52:5–9

    Article  CAS  PubMed  Google Scholar 

  41. Chen L, Jiang W, Huang J, He BC, Zuo GW, Zhang W, Luo Q, Shi Q, Zhang BQ, Wagner ER (2010) Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation. J Bone Miner Res 25(11):2447–2459

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Balazs R (2014) Epigenetic mechanisms in Alzheimer's disease. Degener Neurol Neuromuscul Dis 4:85–102

    Google Scholar 

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Conflict of interest

No potential conflicts of interest were disclosed.

Ethical standards

All studies have been approved by the ethics committee of Shanghai First People’s Hospital and performed in accordance with the ethical standards.

Informed consent

All patients gave written informed consent to the procedure. The studies have been approved by The Ethics Committee of Shanghai First People’s Hospital and performed in accordance with the ethical standards.

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Correspondence to M. D. Jie Tao.

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Zhou, Z., Gao, M., Liu, Q. et al. Comprehensive transcriptome analysis of mesenchymal stem cells in elderly patients with osteoporosis. Aging Clin Exp Res 27, 595–601 (2015). https://doi.org/10.1007/s40520-015-0346-z

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  • DOI: https://doi.org/10.1007/s40520-015-0346-z

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