Role of nanoparticles in osteogenic differentiation of bone marrow mesenchymal stem cells

  • Nadia S. MahmoudEmail author
  • Hanaa H. Ahmed
  • Mohamed R. Mohamed
  • Khalda S. Amr
  • Hadeer A. Aglan
  • Mohamed A. M. Ali
  • Mohamed A. Tantawy
Original Article


The present study aimed to investigate the osteoinductive potentiality of some selected nanostructures; Hydroxyapatite (HA-NPs), Gold (Au-NPs), Chitosan (C-NPs), Gold/hydroxyapatite (Au/HA-NPs) and Chitosan/hydroxyapatite (CH-NPs) on bone marrow- derived mesenchymal stem cells (BM-MSCs). These nanostructures were characterized using transmission electron microscope and Zetasizer. MSCs were isolated from bone marrow of rat femur bones and their identity was documented by morphology, flow cytometry and multi-potency capacity. The influence of the selected nanostructures on the viability, osteogenic differentiation and subsequent matrix mineralization of BM-MSCs was determined by MTT assay, molecular genetic analysis and alizarin red S staining, respectively. MTT analysis revealed insignificant toxicity of the tested nanostructures on BM-MSCs at concentrations ranged from 2 to 25 µg/ml over 48 h and 72 h incubation period. Notably, the tested nanostructures potentiate the osteogenic differentiation of BM-MSCs as evidenced by a prominent over-expression of runt-related transcription factor 2 (Runx-2) and bone morphogenetic protein 2 (BMP-2) genes after 7 days incubation. Moreover, the tested nanostructures induced matrix mineralization of BM-MSCs after 21 days as manifested by the formation of calcium nodules stained with alizarin red S. Conclusively, these data provide a compelling evidence for the functionality of the studied nanostructures as osteoinductive materials motivating the differentiation of BM-MSCs into osteoblasts with the most prominent effect observed with Au-NPs and Au/HA-NPs, followed by CH-NPs.


Bone marrow mesenchymal stem cells Osteogenic differentiation Hydroxyapatite Gold Chitosan Nanoparticles 



The authors gratefully acknowledge the financial support of the National Research Centre, Egypt.


This work was financially supported by the National Research Centre, Egypt (Thesis fund No. 71511).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Akahane M, Ueha T, Shimizu T, Inagaki Y, Kido A, Imamura T, Kawate K, Tanaka Y (2012) Increased osteogenesis with hydroxyapatite constructs combined with serially-passaged bone marrow-derived mesenchymal stem cells. Stem Cell Discov 2:133–140CrossRefGoogle Scholar
  2. Bayati V, Hashemitabar M, Gazor R, Nejatbakhsh R, Bijannejad D (2013) Expression of surface markers and myogenic potential of rat bone marrow and adipose-derived stem cells: a comparative study. Anat Cell Biol 46:113–121PubMedPubMedCentralCrossRefGoogle Scholar
  3. Benoit DSW, Collins SD, Anseth KS (2007) Multifunctional hydrogels that promote osteogenic human mesenchymal stem cell differentiation through stimulation and sequestering of bone morphogenic protein 2. Adv Funct Mater 17:2085–2093PubMedPubMedCentralCrossRefGoogle Scholar
  4. Cai Y, Liu Y, Yan W, Hu Q, Tao J, Zhang M, Shic Z, Tang R (2007) Role of hydroxyapatite nanoparticle size in bone cell proliferation. J Mater Chem 17:3780–3787CrossRefGoogle Scholar
  5. Chen Y, Huang Z, Li X, Li S, Zhou Z, Zhang Y, Feng Q, Yu B (2012) In vitro biocompatibility and osteoblast differentiation of an injectable chitosan/nano-hydroxyapatite/collagen scaffold. J Nanomater 2012:1–6. CrossRefGoogle Scholar
  6. Chen H, Dorrigan A, Saad S, Hare DJ, Cortie MB, Valenzuela SM (2013) In vivo study of spherical gold nanoparticles: inflammatory effects and distribution in mice. PLoS ONE 8:e58208PubMedPubMedCentralCrossRefGoogle Scholar
  7. Choi SY, Song MS, Ryu PD, Lam ATN, Joo S-W, Lee SY (2015) Gold nanoparticles promote osteogenic differentiation in human adipose-derived mesenchymal stem cells through the Wnt/β-catenin signaling pathway. Int J Nanomed 10:4383–4392Google Scholar
  8. Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD (2005) Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1:325–327PubMedCrossRefGoogle Scholar
  9. Crisan L, Crisan B, Soritau O, Baciut M, Biris AR, Baciut G, Lucaciu O (2015) In vitro study of biocompatibility of a graphene composite with gold nanoparticles and hydroxyapatite on human osteoblasts. J Appl Toxicol 35:1200–1210PubMedCrossRefGoogle Scholar
  10. Dhivya S, Saravanan S, Sastry TP, Selvamurugan N (2015) Nanohydroxyapatite-reinforced chitosan composite hydrogel for bone tissue repair in vitro and in vivo. J Nanobiotechnol 13:40CrossRefGoogle Scholar
  11. Eliaz N, Metoki N (2017) Calcium phosphate bioceramics: a review of their history, structure, properties, coating technologies and biomedical applications. Mater (Basel) 10:e334. CrossRefGoogle Scholar
  12. Ferreira dos Santos C, Gomes PS, Almeida MM, Willinger M, Franke R, Fernandescd MH, El Costa M (2015) Gold-dotted hydroxyapatite nanoparticles as multifunctional platforms for medical applications. RSC Adv 5:69184–69195CrossRefGoogle Scholar
  13. Fitzsimmons REB, Mazurek MS, Soos A, Simmons CA (2018) Mesenchymal stromal/stem cells in regenerative medicine and tissue engineering. Stem Cells Int 2018:1–16. CrossRefGoogle Scholar
  14. Freese C, Gibson MI, Klok HA, Unger RE, Kirkpatrick CJ (2012a) Size- and coating-dependent uptake of polymer-coated gold nanoparticles in primary human dermal microvascular endothelial cells. Biomacromol 13:1533–1543CrossRefGoogle Scholar
  15. Freese C, Uboldi C, Gibson MI, Unger RE, Weksler BB, Romero IA, Couraud P-O, Kirkpatrick CJ (2012b) Uptake and cytotoxicity of citrate-coated gold nanospheres: comparative studies on human endothelial and epithelial cells. Part. Fibre Toxicol 9:23CrossRefGoogle Scholar
  16. Grenha A, Seijo B, Remunan-Lopez C (2005) Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci 25:427–437PubMedCrossRefGoogle Scholar
  17. Guidotti S, Facchini A, Platano D, Olivotto E, Minguzzi M, Trisolino G, Filrdo G, Cetrullo S, Tantini B, Martucci E, Facchini A, Flamigni F, Borzi RM (2013) Enhanced osteoblastogenesis of adipose-derived stem cells on spermine delivery via beta-catenin activation. Stem Cells Dev 22:1588–1601PubMedCrossRefGoogle Scholar
  18. Hamidouche Z, Hay E, Vaudin P, Charbord P, Schule R, Marie PJ, Fromigue O (2008) FHL2 mediates dexamethasone-induced mesenchymal cell differentiation into osteoblasts by activating Wnt/beta-catenin signalingdependent Runx2 expression. Faseb J 22:3813–3822PubMedCrossRefGoogle Scholar
  19. Heo DN, Ko WK, Bae MS, Lee JB, Lee D-W, Byun W, Lee CH, Kim E-C, Jung B-Y, Kwon K (2014) Enhanced bone regeneration with a gold nanoparticle–hydrogel complex. J Mater Chem B Mater Biol Med 2:1584–1594CrossRefGoogle Scholar
  20. Hu J, Zhou Y, Huang L, Liu J, Lu H (2014) Effect of nano-hydroxyapatite coating on the osteoinductivity of porous biphasic calcium phosphate ceramics. BMC Musculoskelet Disord 15:114PubMedPubMedCentralCrossRefGoogle Scholar
  21. Huang GT, Gronthos S, Shi S (2009) Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 88:792–806PubMedPubMedCentralCrossRefGoogle Scholar
  22. Huang Y, Zhou G, Zheng L, Liu H, Niu X, Fan Y (2012) Micro-/nano- sized hydroxyapatite directs differentiation of rat bone marrow derived mesenchymal stem cells towards an osteoblast lineage. Nanoscale 4:2484–2490PubMedCrossRefGoogle Scholar
  23. Hunter RJ (1981) Zeta potential in colloid science: principles and applications. Academic Press, New YorkGoogle Scholar
  24. Iswanti FC, Nurulita I, Djauzi S, Sadikin M, Witarto AB, Yamazaki T (2019) Preparation, characterization, and evaluation of chitosan-based nanoparticles as CpG ODN carriers. Biotechnol Biotechnol Equip. CrossRefGoogle Scholar
  25. Jones GL, Motta A, Marshall MJ, El Haj AJ, Cartmell SH (2009) Osteoblast: osteoclast co-cultures on silk fibroin, chitosan and PLLA films. Biomaterials 30:5376–5384PubMedCrossRefGoogle Scholar
  26. Khan JA, Pillai B, Das TK, Singh Y, Maiti S (2007) Molecular effects of uptake of gold nanoparticles in HeLa cells. ChemBioChem 8:1237–1240PubMedCrossRefGoogle Scholar
  27. Khatiwala CB, Kim PD, Peyton SR, Putnam AJ (2009) ECM compliance regulates osteogenesis by influencing MAPK signaling downstream of RhoA and ROCK. J Bone Miner Res 24:886–898PubMedCrossRefGoogle Scholar
  28. Kim K, Dean D, Lu A, Mikos AG, Fisher JP (2011) Early osteogenic signal expression of rat bone marrow stromal cells is influenced by both hydroxyapatite nanoparticle content and initial cell seeding density in biodegradable nanocomposite scaffolds. Acta Biomater 7:1249–1264. CrossRefPubMedGoogle Scholar
  29. Ko WK, Heo DN, Moon HJ, Lee SJ, Bae MS, Lee JB, Sun IC, Jeon HB, Park HK, Kwon IK (2015) The effect of gold nanoparticle size on osteogenic differentiation of adipose-derived stem cells. J Colloid Interface Sci 438:68–76. CrossRefPubMedGoogle Scholar
  30. Komori T (2003) Requisite roles of Runx2 and Cbfb in skeletal development. J Bone Miner Metab 21:193–197PubMedGoogle Scholar
  31. Levengood SKL, Zhang M (2014) Chitosan-based scaffolds for bone tissue engineering. J Mater Chem B 2:3161–3184. CrossRefPubMedPubMedCentralGoogle Scholar
  32. Li J, Li JJ, Zhang J, Wang X, Kawazoea N, Chen G (2016) Gold nanoparticle size and shape influence on osteogenesis of mesenchymal stem cells. Nanoscale 8:7992–8007PubMedCrossRefGoogle Scholar
  33. Lian JB, Stein GS, Javed A, Van Wijnen AJ, Stein L, Montecino M, Hassan MQ, Gaur T, Lengner CJ, Young DW (2006) Networks and hubs for the transcriptional control of osteoblastogenesis. Rev Endocr Metab Disord 7:1–16PubMedCrossRefGoogle Scholar
  34. Linard C, Brachet M, L’homme B, Strup-Perrot C, Busson E, Bonneau M, Lataillade JJ, Bey E, Benderitter M (2018) Long-term effectiveness of local BM-MSCs for skeletal muscle regeneration: a proof of concept obtained on a pig model of severe radiation burn. Stem Cell Res Ther 9:299. CrossRefPubMedPubMedCentralGoogle Scholar
  35. Liu DD, Yi CQ, Zhang DW, Zhang JC, Yang MS (2010a) Inhibition of proliferation and differentiation of mesenchymal stern cells by carboxylated carbon nanotubes. ACS Nano 4:2185–2195PubMedCrossRefGoogle Scholar
  36. Liu DD, Zhang JC, Yi CQ, Yang M (2010b) The effects of gold nanoparticles on the proliferation, differentiation, and mineralization function of MC3T3-E1 cells in vitro. Chin Sci Bull 55:1013–1019. CrossRefGoogle Scholar
  37. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408CrossRefGoogle Scholar
  38. Lock J, Liu H (2011) Nanomaterials enhance osteogenic differentiation of human mesenchymal stem cells similar to a short peptide of BMP-7. Int J Nanomed 6:2769–2777Google Scholar
  39. Lu Z, Roohani-Esfahani S-I, Kwok PCL, Zreiqat H (2011) Osteoblasts on rod shaped hydroxyapatite nanoparticles incorporated pcl film provide an optimal osteogenic niche for stem cell differentiation. Tissue Eng Part A 17:1651–1661PubMedCrossRefGoogle Scholar
  40. Ma X-Y, Feng Y-F, Wang T-S, Le WI, Li X, Zhou D-P, Wen X-X, Yu H-L, Xiang L-B, Wang L (2018) Involvement of FAK-mediated BMP-2/Smad pathway in mediating osteoblast adhesion and differentiation on nano-HA/chitosan composite coated titanium implant under diabetic conditions. Biomater Sci 6:225–238CrossRefGoogle Scholar
  41. Macri-Pellizzeri L, De Melo N, Ahmed I, Grant D, Scammell B, Sottile V (2018) Live quantitative monitoring of mineral depositionin stem cells using tetracycline hydrochloride. Tissue Eng Part C Methods 24:171–178PubMedPubMedCentralCrossRefGoogle Scholar
  42. Mahla RS (2016) Stem cells applications in regenerative medicine and disease therapeutics. Int J Cell Biol 2016:6940283PubMedPubMedCentralCrossRefGoogle Scholar
  43. Mansour SF, El-dek SI, Ahmed MK (2017) Physico-mechanical and morphological features of zirconia substituted hydroxyapatite nanocrystals. Sci Rep 7:43202PubMedPubMedCentralCrossRefGoogle Scholar
  44. Mauricio MD, Guerra-Ojeda S, Marchio P, Valles SL, Aldasoro M, Escribano-Lopez I, Herance JR, Rocha M, Vila JM, Victor VM (2018) Nanoparticles in medicine: a focus on vascular oxidative stress. Oxid Med Cell Longev 2018:6231482. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Müller P, Lemcke H, David R (2018) Stem cell therapy in heart diseases – cell types, mechanisms and improvement strategies. Cell Physiol Biochem 48:2607–2655. CrossRefPubMedGoogle Scholar
  46. Muller KH, Motskin M, Philpott AJ, Routh AF, Shanahan CM, Duer MJ, Skepper JN (2014) The effect of particle agglomeration on the formation of a surface-connected compartment induced by hydroxyapatite nanoparticles in human monocyte-derived macrophages. Biomater 35:1074–1088.CrossRefGoogle Scholar
  47. Muniswami DM, Kanthakumar P, Kanakasabapathy I, Tharion G (2018) Motor recovery after transplantation of bone marrow mesenchymal stem cells in rat models of spinal cord injury. Ann Neurosci 25:126–140PubMedPubMedCentralCrossRefGoogle Scholar
  48. Naruphontjirakul P, Tsigkou O, Li S, Porter AE, Jones JR (2019) Human mesenchymal stem cells differentiate into an osteogenic lineage in presence of strontium containing bioactive glass nanoparticles. Acta Biomater 90:373–392. CrossRefPubMedGoogle Scholar
  49. Nguyen AK, Patel R, Noble JM, Zheng J, Narayan RJ, Kumar G, Goering PL (2019) Effects of subcytotoxic exposure of silver nanoparticles on osteogenic differentiation of human bone marrow stem cells. Appl In Vitro Toxicol 5:123–133. CrossRefGoogle Scholar
  50. Niu W, Guo Y, Xue Y, Chen M, Wang M, Cheng W, Lei B (2019) Monodisperse branched molybdenum-based bioactive nanoparticles significantly promote osteogenic differentiation of adipose-derived stem cells. Part Part Syst Charact 36:1900105. CrossRefGoogle Scholar
  51. Okada M, Matsumoto T (2015) Synthesis and modification of apatite nanoparticles for use in dental and medical applications. Jpn Dent Sci Rev 51:85–95CrossRefGoogle Scholar
  52. Peng H, Yin Z, Liu H, Chen X, Feng B, Yuan H, Su B, Ouyang H, Zhang Y (2012) Electrospun biomimetic scaffold of hydroxyapatite/chitosan supports enhanced osteogenic differentiation of mMSCs. Nanotechnology 23:485102. CrossRefPubMedGoogle Scholar
  53. Phimphilai M, Zhao Z, Boules H, Roca H, Franceschi RT (2006) BMP signaling is required for RUNX 2-dependent induction of the osteoblast phenotype. J Bone Miner Res 21:637–646PubMedPubMedCentralCrossRefGoogle Scholar
  54. Pissuwan D, Cortie CH, Valenzuela SM, Cortie MB (2007a) Gold nanosphere antibody conjugates for hyperthermal therapeutic applications. Gold Bull 40:121–129CrossRefGoogle Scholar
  55. Pissuwan D, Valenzuela SM, Killingsworth MC, Xu XD, Cortie MB (2007b) Targeted destruction of murine macrophage cells with bioconjugated gold nanorods. J Nanopart Res 9:1109–1124CrossRefGoogle Scholar
  56. Prajatelistia E, Lim C, Oh DX, Jun SH, Hwang DS (2015) Chitosan and hydroxyapatite composite cross-linked by dopamine has improved anisotropic hydroxyapatite growth and wet mechanical properties. Eng Life Sci 15:254–261CrossRefGoogle Scholar
  57. Remya NS, Syama S, Gayathri V, Varma HK, Mohanan PV (2014) An in vitro study on the interaction of hydroxyapatite nanoparticles and bone marrow mesenchymal stem cells for assessing the toxicological behavior. Colloids Surf B Biointerfaces 117:389–397PubMedCrossRefGoogle Scholar
  58. Rodríguez-Vázquez M, Vega-Ruiz B, Ramos-Zúñiga R, Saldaña-Koppel DA, Quiñones-Olvera LF (2015) Chitosan and its potential use as a scaffold for tissue engineering in regenerative medicine. Biomed Res Int 2015:821279PubMedPubMedCentralCrossRefGoogle Scholar
  59. Rogina A, Antunović M, Pribolšan L, Mihalić KC, Vukasović A, Ivković A, Marijanović I, Ferrer GG, Ivanković M, Ivanković H (2017) human mesenchymal stem cells differentiation regulated by hydroxyapatite content within chitosan-based scaffolds under perfusion conditions. Polymers 9:387PubMedCentralCrossRefPubMedGoogle Scholar
  60. Roohani-Esfahani SI, Nouri-Khorasani S, Lu Z, Appleyard R, Zreiqat H (2010) The influence hydroxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coated with hydroxyapatite PCL composites. Biomaterials 31:5509CrossRefGoogle Scholar
  61. Sangeetha P, Maiti SK, Mohan D, Shivaraju S, Raguvaran R, Abu Rafee M, Bindhuja BV, Kumar N, Raguvanshi PDS (2017) Mesenchymal stem cells derived from rat bone marrow (rBM-MSCs): techniques for isolation, expansion and differentiation. J Stem Cell Res Ther 3:272–277. CrossRefGoogle Scholar
  62. Singh P, Pandit S, Mokkapati VRSS, Garg A, Ravikumar V, Mijakovic I (2018) Gold nanoparticles in diagnostics and therapeutics for human cancer. Int J Mol Sci 19:1979. CrossRefPubMedCentralPubMedGoogle Scholar
  63. Sobczak-Kupiec A, Tyliszczak B, Krupa-Żuczek K, Malina D, Piątkowski M, Wzorek Z (2014) Gold nanoparticles as a modifying agent of ceramic-polymer composites. Arch Metall Mater 59:1009CrossRefGoogle Scholar
  64. Tada H, Nemoto E, Foster BL, Somerman MJ, Shimauchi H (2011) Phosphate increases bone morphogenetic protein-2 expression through cAMP dependent protein kinase and ERK1/2 pathways in human dental pulp cells. Bone 48:1409–1416PubMedCrossRefGoogle Scholar
  65. Ullah I, Subbarao RB, Rho GJ (2015) Human mesenchymal stem cells - current trends and future prospective. Biosci Rep 35:e00191. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Uskoković V, Desai TA (2014) In vitro analysis of nanoparticulate hydroxyapatite/chitosan composites as potential drug delivery platforms for the sustained release of antibiotics in the treatment of osteomyelitis. J Pharm Sci 103:567–579. CrossRefPubMedGoogle Scholar
  67. Van Meerloo J, Kaspers GJL, Cloos J (2011) Cell sensitivity assays: the MTT assay. Methods Mol Biol 731:237–245. CrossRefPubMedGoogle Scholar
  68. Vandiver J, Dean D, Patel N, Bonfield W, Ortiz C (2005) Nanoscale variation in surface charge of synthetic hydroxyapatite detected by chemically and spatially specific high-resolution force spectroscopy. Biomaterials 26:271–283PubMedCrossRefGoogle Scholar
  69. Vater C, Kasten P, Stiehler M (2011) Culture media for the differentiation of mesenchymal stromal cells. Acta Biomater 7:463–477PubMedCrossRefGoogle Scholar
  70. Verma A, Stellacci F (2010) Effect of surface properties on nanoparticle-cell interactions. Small 6:12–21PubMedCrossRefGoogle Scholar
  71. Wan A-J, Sun Y, Li W-T, Li H-L (2007) transmission electron microscopy and electron diffraction study of BSA-loaded quaternized chitosan nanoparticles. J Biomed Mater Res B Appl Biomater 86:197–207Google Scholar
  72. Wang FS, Wang CJ, Sheen-Chen SM, Kuo YR, Chen RF, Yang KD (2002) Superoxide mediates shock wave induction of ERK-dependent osteogenic transcription factor (CBFA1) and mesenchymal cell differentiation toward osteoprogenitors. J Biol Chem 277:10931–10937PubMedCrossRefGoogle Scholar
  73. Wang C, Meng H, Wang X, Zhao C, Peng J, Wang Y (2016) Differentiation of bone marrow mesenchymal stem cells in osteoblasts and adipocytes and its role in treatment of osteoporosis. Med Sci Monit 22:226–233PubMedPubMedCentralCrossRefGoogle Scholar
  74. Wang C, Cao X, Zhang Y (2017a) A novel bioactive osteogenesis scaffold delivers ascorbic acid, β-glycerophosphate, and dexamethasone in vivo to promote bone regeneration. Oncotarget 8:31612–31625. CrossRefPubMedPubMedCentralGoogle Scholar
  75. Wang Q, Chen B, Ma F, Lin S, Cao M, Li Y, Gu N (2017b) Magnetic iron oxide nanoparticles accelerate osteogenic differentiation of mesenchymal stem cells via modulation of long noncoding RNA INZEB2. Nano Res 10:626–642. CrossRefGoogle Scholar
  76. Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370PubMedCrossRefGoogle Scholar
  77. Xia Y, Chen H, Zhang F, Bao C, Weir MD, Reynolds MA, Ma J, Gu N, Xu HHK (2018) Gold nanoparticles in injectable calcium phosphate cement enhance osteogenic differentiation of human dental pulp stem cells. Nanomedicine 14:35–45PubMedCrossRefGoogle Scholar
  78. Xiao G, Jiang D, Thomas P, Benson MD, Guan K, Karsenty G, Franceschi RT (2000) MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J Biol Chem 275:4453–4459PubMedCrossRefGoogle Scholar
  79. Yang K, Cao W, Hao X, Xue X, Zhao J, Liu J, Zhao Y, Meng J, Sun B, Zhang J (2013) Metallofullerene nanoparticles promote osteogenic differentiation of bone marrow stromal cells through BMP signaling pathway. Nanoscale 5:1205–1212PubMedCrossRefGoogle Scholar
  80. Yao W, Lane NE (2015) Targeted delivery of mesenchymal stem cells to the bone. Bone 70:62–65PubMedCrossRefGoogle Scholar
  81. Yao W, Guan M, Jia J, Dai W, Lay YA, Amugongo S, Liu R, Olivos D, Saunders M, Lam KS, Nolta J, Olvera D, Ritchie RO, Lane NE (2013) Reversing bone loss by directing mesenchymal stem cells to bone. Stem Cells 31:2003–2014PubMedPubMedCentralCrossRefGoogle Scholar
  82. Yi C, Liu D, Fong CC, Zhang J, Yang M (2010) Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. ACS Nano 4:6439–6448. CrossRefPubMedGoogle Scholar
  83. Yuan T, Luo H, Tan J, Fan H, Zhang X (2011) The effect of stress and tissue fluid microenvironment on allogeneic chondrocytes in vivo and the immunological properties of engineered cartilage. Biomaterials 32:6017–6024PubMedCrossRefGoogle Scholar
  84. Yubao L, Klein CPAT, de Wijn J, Wolke J, de Groot K (1993) Morphology and phase structure of nanograde boneapatite-like rodshaped crystals. In: Ducheyne P, Christiansen D (eds) Bioceramics. Butterworth-Heinemann, Philadelphia, pp 173–178Google Scholar
  85. Yusop N, Battersby P, Alraies A, Sloan AJ, Moseley R, Waddington RJ (2018) Isolation and characterisation of mesenchymal stem cells from rat bone marrow and the endosteal niche: a comparative study. Stem Cells Int 2018:1–14CrossRefGoogle Scholar
  86. Zainol I, Zakaria FA, Saliman MR, Derman MA (2008) Preparation and characterisation of chitosan/nano hydroxyapatite composites. J Solid State Sci Technol 16:153–159Google Scholar
  87. Zhang D, Liu D, Zhang J, Fong C, Yang M (2014a) Gold nanoparticles stimulate differentiation and mineralization of primary osteoblasts through the ERK/MAPK signaling pathway. Mater Sci Eng C Mater Biol Appl 42:70–77PubMedCrossRefGoogle Scholar
  88. Zhang X, Guo J, Zhou Y, Wu G (2014b) The roles of bone morphogenetic proteins and their signaling in the osteogenesis of adipose-derived stem cells. Tissue Eng Part B 20:84–92CrossRefGoogle Scholar
  89. Zhao F, Zhao Y, Liu Y, Chang X, Chen C, Zhao Y (2011) Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 7:1322–1337PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Hormones Department, Medical Research DivisionNational Research CentreDokki, GizaEgypt
  2. 2.Stem Cells LabCenter of Excellence for Advanced Sciences, National Research CentreDokki, GizaEgypt
  3. 3.Biochemistry Department, Faculty of ScienceAin Shams UniversityCairoEgypt
  4. 4.Medical Molecular Genetics Department, Human Genetics and Genome Researches DivisionNational Research CentreDokki, GizaEgypt

Personalised recommendations