Potential Osteoinductive Effects of Hydroxyapatite Nanoparticles on Mesenchymal Stem Cells by Endothelial Cell Interaction
Tóm tắt
Nano-hydroxyapatite (nano-HA) has attracted substantial attention in the field of regenerative medicine. Endothelial cell (EC)-mesenchymal stem cell (MSC) interactions are necessary for bone reconstruction, but the manner in which nano-HA interacts in this process remains unknown. Herein, we investigated the cytotoxicity and osteoinductive effects of HA nanoparticles (HANPs) on MSCs using an indirect co-culture model mediated by ECs and highlighted the underlying mechanisms. It was found that at a subcytotoxic dose, HANPs increased the viability and expression of osteoblast genes, as well as mineralized nodules and alkaline phosphatase production of MSCs. These phenomena relied on HIF-1α secreted by ECs, which triggered the ERK1/2 signaling cascade. In addition, a two-stage cell-lineage mathematical model was established to quantitatively analyze the impact of HIF-1α on the osteogenic differentiation of MSCs. It demonstrated that HIF-1α exerted a dose-dependent stimulatory effect on the osteogenic differentiation rate of MSCs up to 1500 pg/mL, which was in agreement with the above results. Our data implied that cooperative interactions between HANPs, ECs, and MSCs likely serve to stimulate bone regeneration. Furthermore, the two-stage cell-lineage model is helpful in vitro system for assessing the potential influence of effector molecules in bone tissue engineering.
Từ khóa
Tài liệu tham khảo
Liu H et al (2018) Endothelial progenitor cells improve the therapeutic effect of mesenchymal stem cell sheets on irradiated bone defect repair in a rat model. J Transl Med 16(1):137
Du J et al (2018) Effect of hydroxyapatite fillers on the mechanical properties and osteogenesis capacity of bio-based polyurethane composite scaffolds. J Mech Behav Biomed Mater 88:150–159
Garcia-Gareta E, Coathup MJ, Blunn GW (2015) Osteoinduction of bone grafting materials for bone repair and regeneration. Bone 81:112–121
Eriksson M et al (2011) Transparent hydroxyapatite ceramics with nanograin structure prepared by high pressure spark plasma sintering at the minimized sintering temperature. J Eur Ceram Soc 31(9):1533–1540
Shi X et al (2018) Endocytic mechanisms and osteoinductive profile of hydroxyapatite nanoparticles in human umbilical cord Wharton’s jelly-derived mesenchymal stem cells. Int J Nanomed 13:1457–1470
Wang R et al (2019) Nano-hydroxyapatite modulates osteoblast differentiation through autophagy induction via mTOR signaling pathway. J Biomed Nanotechnol 15(2):405–415
Shi Z et al (2009) Size effect of hydroxyapatite nanoparticles on proliferation and apoptosis of osteoblast-like cells. Acta Biomater 5(1):338–345
Dua R et al (2016) Integration of stem cell to chondrocyte-derived cartilage matrix in healthy and osteoarthritic states in the presence of hydroxyapatite nanoparticles. PLoS ONE 11(2):e0149121
Shi X et al (2017) Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway. Int J Nanomed 12:5781–5795
Rafii S, Butler JM, Ding BS (2016) Angiocrine functions of organ-specific endothelial cells. Nature 529(7586):316–325
Kaigler D et al (2005) Endothelial cell modulation of bone marrow stromal cell osteogenic potential. FASEB J 19(6):665–667
Assis-Ribas T et al (2018) Extracellular matrix dynamics during mesenchymal stem cells differentiation. Dev Biol 437(2):63–74
Tsai TL et al (2015) Endothelial cells direct human mesenchymal stem cells for osteo- and chondro-lineage differentiation through endothelin-1 and AKT signaling. Stem Cell Res Ther 6:88
Saleh FA et al (2011) Regulation of mesenchymal stem cell activity by endothelial cells. Stem Cells Dev 20(3):391–403
Pezzatini S et al (2007) Nanostructured HA crystals up-regulate FGF-2 expression and activity in microvascular endothelium promoting angiogenesis. Bone 41(4):523–534
Qiao C et al (2008) Human mesenchymal stem cells isolated from the umbilical cord. Cell Biol Int 32(1):8–15
Liu X, Sun JA (2010) Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kappa B pathways. Biomaterials 31(32):8198–8209
Chou CS et al (2010) Spatial dynamics of multistage cell lineages in tissue stratification. Biophys J 99(10):3145–3154
Zhu H, Wang M-X, Lai P-Y (2018) General two-species interacting Lotka–Volterra system: population dynamics and wave propagation. Phys Rev E 97(5):052413
Doostmohammadi A et al (2011) Bioactive glass nanoparticles with negative zeta potential. Ceram Int 37(7):2311–2316
Kobayashi T, Nakamura S, Yamashita K (2001) Enhanced osteobonding by negative surface charges of electrically polarized hydroxyapatite. J Biomed Mater Res 57(4):477–484
Shang L, Nienhaus K, Nienhaus GU (2014) Engineered nanoparticles interacting with cells: size matters. J Nanobiotechnol 12:5
Amani H et al (2019) Controlling cell behavior through the design of biomaterial surfaces: a focus on surface modification techniques. Adv Mater Interfaces 6(13):1900572
Hwang JH et al (2019) Artificial cellular nano-environment composed of collagen-based nanofilm promotes osteogenic differentiation of mesenchymal stem cells. Acta Biomater 86:247–256
Wu Z et al (2018) TiO2 nanotubes enhance vascularization and osteogenic differentiation through stimulating interactions between bone marrow stromal cells and endothelial cells. J Biomed Nanotechnol 14(4):765–777
Liu X, Sun J (2014) Potential proinflammatory effects of hydroxyapatite nanoparticles on endothelial cells in a monocyte-endothelial cell coculture model. Int J Nanomed 9:1261–1273
Jiang W et al (2008) Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol 3(3):145–150
Yang L et al (2014) Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation. Proc Natl Acad Sci USA 111(33):12097–12102
Zou D et al (2011) In vitro study of enhanced osteogenesis induced by HIF-1alpha-transduced bone marrow stem cells. Cell Prolif 44(3):234–243
Nunez-Toldra R et al (2017) Improvement of osteogenesis in dental pulp pluripotent-like stem cells by oligopeptide-modified poly(beta-amino ester)s. Acta Biomater 53:152–164
Stegen S et al (2016) Adequate hypoxia inducible factor 1alpha signaling is indispensable for bone regeneration. Bone 87:176–186
Lampert FM et al (2016) Overexpression of Hif-1alpha in mesenchymal stem cells affects cell-autonomous angiogenic and osteogenic parameters. J Cell Biochem 117(3):760–768
Heikal L et al (2018) Assessment of HIF-1alpha expression and release following endothelial injury in-vitro and in-vivo. Mol Med 24(1):22
Tsuboi I et al (2015) Impaired expression of HIF-2alpha induces compensatory expression of HIF-1alpha for the recovery from anemia. J Cell Physiol 230(7):1534–1548
Murakami J et al (2017) Vascular endothelial growth factor-C induces osteogenic differentiation of human mesenchymal stem cells through the ERK and RUNX2 pathway. Biochem Biophys Res Commun 484(3):710–718
Ishii M et al (2019) Vascular endothelial growth factor-C promotes human mesenchymal stem cell migration via an ERK-and FAK-dependent mechanism. Mol Cell Biochem 455(1–2):185–193
Tamama K et al (2006) Epidermal growth factor as a candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells. Stem Cells 24(3):686–695
Kapitanov G (2012) A mathematical model of cancer stem cell lineage population dynamics with mutation accumulation and telomere length hierarchies. Math Model Nat Phenom 7(7):136–165