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Current Stem Cell Research & Therapy


ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Mesenchymal Stem Cells Differentiation: Mitochondria Matter in Osteogenesis or Adipogenesis Direction

Author(s): Kun Ji , Ling Ding, Xi Chen , Yun Dai, Fangfang Sun, Guofeng Wu * and Wei Lu*

Volume 15, Issue 7, 2020

Page: [602 - 606] Pages: 5

DOI: 10.2174/1574888X15666200324165655

Price: $65


Mesenchymal Stem Cells (MSCs) exhibit enormous therapeutic potential because of their indispensable regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties. MSCs can best differentiate into mesodermal cell lineages, including osteoblasts, adipocytes, muscle cells, endothelial cells and chondrocytes. Specific differentiation of MSCs could be induced through limited conditions. In addition to the relevant differentiation factors, drastic changes also occur in the microenvironment to conduct it in an optimal manner for particular differentiation. Recent evidence suggests that the mitochondria participate in the regulating of direction and process of MSCs differentiation. Therefore, our current review focuses on how mitochondria participate in both osteogenesis and adipogenesis of MSC differentiation. Besides that, in our current review, we try to provide a further understanding of the relationship between the behavior of mitochondria and the direction of MSC differentiation, which could optimize current cellular culturing protocols for further facilitating tissue engineering by adjusting specific conditions of stem cells.

Keywords: Mitochondria, mesenchymal stem cells, osteogenesis, adipogenesis, metabolism, ageing, hypoxia.

Karaöz E, Okçu A, Gacar G, Sağlam O, Yürüker S, Kenar H. A comprehensive characterization study of human bone marrow mscs with an emphasis on molecular and ultrastructural properties. J Cell Physiol 2011; 226(5): 1367-82.
[] [PMID: 20945392]
Baxter MA, Wynn RF, Jowitt SN, Wraith JE, Fairbairn LJ, Bellantuono I. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells 2004; 22(5): 675-82.
[] [PMID: 15342932]
Piryaei A, Valojerdi MR, Shahsavani M, Baharvand H. Differentiation of Bone Marrow-derived Mesenchymal Stem Cells into Hepatocyte-like Cells on Nanofibers and Their Transplantation into a Carbon Tetrachloride-Induced Liver Fibrosis Model. Stem Cell Rev. Reports 2011.
Madeira VMC. Overview of mitochondrial bioenergetics. Methods Mol Biol 2018; 1782: 1-6.
[] [PMID: 29850991]
Quinn KP, Sridharan GV, Hayden RS, Kaplan DL, Lee K, Georgakoudi I. Quantitative metabolic imaging using endogenous fluorescence to detect stem cell differentiation. Sci Rep 2013; 3: 3432.
[] [PMID: 24305550]
Lane N, Martin W. The energetics of genome complexity. Nature 2010; 467(7318): 929-34.
[] [PMID: 20962839]
Pei DD, Sun JL, Zhu CH, et al. Contribution of Mitophagy to Cell-Mediated Mineralization: Revisiting a 50-Year-Old Conundrum. Adv Sci (Weinh) 2018; 5(10): 1800873
[] [PMID: 30356983]
Li Q, Gao Z, Chen Y, Guan MX. The role of mitochondria in osteogenic, adipogenic and chondrogenic differentiation of mesenchymal stem cells. Protein Cell 2017; 8(6): 439-45.
[] [PMID: 28271444]
Chen C-T, Shih Y-RV, Kuo TK, Lee OK, Wei Y-H. Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells 2008; 26(4): 960-8.
[] [PMID: 18218821]
Agathocleous M, Harris WA. Metabolism in physiological cell proliferation and differentiation. Trends Cell Biol 2013; 23(10): 484-92.
[] [PMID: 23756093]
Min-Wen JC, Jun-Hao ET, Shyh-Chang N. Stem cell mitochondria during aging. Semin Cell Dev Biol 2016; 52: 110-8.
[] [PMID: 26851627]
Hsu YC, Wu YT, Yu TH, Wei YH. Mitochondria in mesenchymal stem cell biology and cell therapy: From cellular differentiation to mitochondrial transfer. Semin Cell Dev Biol 2016; 52: 119-31.
[] [PMID: 26868759]
Owusu-Ansah E, Yavari A, Mandal S, Banerjee U. Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint. Nat Genet 2008; 40(3): 356-61.
[] [PMID: 18246068]
Agathocleous M, Love NK, Randlett O, et al. Metabolic differentiation in the embryonic retina. Nat Cell Biol 2012; 14(8): 859-64.
[] [PMID: 22750943]
Lambertini E, Penolazzi L, Morganti C, et al. Osteogenic differentiation of human MSCs: Specific occupancy of the mitochondrial DNA by NFATc1 transcription factor. Int J Biochem Cell Biol 2015; 64: 212-9.
[] [PMID: 25952151]
Kaelin WG Jr, McKnight SL. Influence of metabolism on epigenetics and disease. Cell 2013; 153(1): 56-69.
[] [PMID: 23540690]
Etchegaray JP, Mostoslavsky R. Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes. Mol Cell 2016; 62(5): 695-711.
[] [PMID: 27259202]
Geissler S, Textor M, Kühnisch J, et al. Functional comparison of chronological and in vitro aging: differential role of the cytoskeleton and mitochondria in mesenchymal stromal cells. PLoS One 2012; 7(12): e52700
[] [PMID: 23285157]
Jun-Hao ET, Gupta RR, Shyh-Chang N. Lin28 and let-7 in the Metabolic Physiology of Aging. Trends Endocrinol Metab 2016; 27(3): 132-41.
[] [PMID: 26811207]
Kim M, Kim C, Choi YS, Kim M, Park C, Suh Y. Age-related alterations in mesenchymal stem cells related to shift in differentiation from osteogenic to adipogenic potential: implication to age-associated bone diseases and defects. Mech Ageing Dev 2012; 133(5): 215-25.
[] [PMID: 22738657]
Adam-Vizi V, Chinopoulos C. Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci 2006; 27(12): 639-45.
[] [PMID: 17056127]
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39(1): 44-84.
[] [PMID: 16978905]
Denu RA, Hematti P. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology. Oxid Med Cell Longev 2016.: 20162989076
[] [PMID: 27413419]
Lin CH, Li NT, Cheng HS, Yen ML. Oxidative stress induces imbalance of adipogenic/osteoblastic lineage commitment in mesenchymal stem cells through decreasing SIRT1 functions. J Cell Mol Med 2018; 22(2): 786-96.
[PMID: 28975701]
Atashi F, Modarressi A, Pepper MS. The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: a review. Stem Cells Dev 2015; 24(10): 1150-63.
[] [PMID: 25603196]
Almeida M, Han L, Martin-Millan M, et al. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem 2007; 282(37): 27285-97.
[] [PMID: 17623659]
Tormos KV, Anso E, Hamanaka RB, et al. Mitochondrial complex III ROS regulate adipocyte differentiation. Cell Metab 2011; 14(4): 537-44.
[] [PMID: 21982713]
Kim KS, Choi HW, Yoon HE, Kim IY. Reactive oxygen species generated by NADPH oxidase 2 and 4 are required for chondrogenic differentiation. J Biol Chem 2010; 285(51): 40294-302.
[] [PMID: 20952384]
Kanda Y, Hinata T, Kang SW, Watanabe Y. Reactive oxygen species mediate adipocyte differentiation in mesenchymal stem cells. Life Sci 2011; 89(7-8): 250-8.
[] [PMID: 21722651]
Lee H, Lee YJ, Choi H, Ko EH, Kim JW. Reactive oxygen species facilitate adipocyte differentiation by accelerating mitotic clonal expansion. J Biol Chem 2009; 284(16): 10601-9.
[] [PMID: 19237544]
Yang LY, Gao JL, Gao T, et al. Toxicity of polyhydroxylated fullerene to mitochondria. J Hazard Mater 2016; 301: 119-26.
[] [PMID: 26348144]
Shen Y, Wu L, Qin D, et al. Carbon black suppresses the osteogenesis of mesenchymal stem cells: the role of mitochondria. Part Fibre Toxicol 2018; 15(1): 16.
[] [PMID: 29650039]
Boyette LB, Creasey OA, Guzik L, Lozito T, Tuan RS. Human bone marrow-derived mesenchymal stem cells display enhanced clonogenicity but impaired differentiation with hypoxic preconditioning. Stem Cells Transl Med 2014; 3(2): 241-54.
[] [PMID: 24436440]
Ejtehadifar M, Shamsasenjan K, Movassaghpour A, et al. The effect of hypoxia on mesenchymal stem cell biology. Adv Pharm Bull 2015; 5(2): 141-9.
[] [PMID: 26236651]
Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 2006; 3(3): 187-97.
[] [PMID: 16517406]
Lee MJ, Chen HT, Ho ML, et al. PPARγ silencing enhances osteogenic differentiation of human adipose-derived mesenchymal stem cells. J Cell Mol Med 2013; 17(9): 1188-93.
[] [PMID: 23937351]
Wagegg M, Gaber T, Lohanatha FL, et al. Hypoxia promotes osteogenesis but suppresses adipogenesis of human mesenchymal stromal cells in a hypoxia-inducible factor-1 dependent manner. PLoS One 2012; 7(9): e46483
[] [PMID: 23029528]
Xu N, Liu H, Qu F, et al. Hypoxia inhibits the differentiation of mesenchymal stem cells into osteoblasts by activation of Notch signaling. Exp Mol Pathol 2013; 94(1): 33-9.
[] [PMID: 22964414]
Deregowski V, Gazzerro E, Priest L, Rydziel S, Canalis E. Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/β-catenin but not bone morphogenetic protein signaling. J Biol Chem 2006; 281(10): 6203-10.
[] [PMID: 16407293]
Hilton MJ, Tu X, Wu X, et al. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med 2008; 14(3): 306-14.
[] [PMID: 18297083]

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