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The Role of Reactive Oxygen Species in Mesenchymal Stem Cell Adipogenic and Osteogenic Differentiation: A Review

Atashi, Fatemeh, Modarressi, Ali, Pepper, Michael S.·2015·Stem Cells and Development
DOI 10.1089/scd.2014.0484PMC PMC4424969
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Abstract

Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering and regenerative medicine. The multipotent stem cell component of MSC isolates is able to differentiate into derivatives of the mesodermal lineage including adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have been described in the regulation of adipogenesis and osteogenesis. However, stimulation of osteogenesis appears to suppress adipogenesis and vice-versa. Increasing evidence implicates a tight regulation of these processes by reactive oxygen species (ROS). ROS are short-lived oxygen-containing molecules that display high chemical reactivity toward DNA, RNA, proteins, and lipids. Mitochondrial complexes I and III, and the NADPH oxidase isoform NOX4 are major sources of ROS production during MSC differentiation. ROS are thought to interact with several pathways that affect the transcription machinery required for MSC differentiation including the Wnt, Hedgehog, and FOXO signaling cascades. On the other hand, elevated levels of ROS, defined as oxidative stress, lead to arrest of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are therefore critical for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS implicated remain to be determined. This review provides a detailed overview of the influence of ROS on adipogenic and osteogenic differentiation in MSCs.

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FIG. 1. Sources of reactive oxygen species (ROS). ROS can be intracellulary generated by mitochondria and diverse NOX isoforms, peroxisome, endoplasmic reticulum (ER), xanthine oxidase, and lipogenase. It can also be applied from exogenous sources. Irrespective of its source, it may cause cell proliferation, differentiation, and/or cell cycle arrest, and this effect appears to be concentration dependent. Color images available online at www.liebertpub.com/scd
FIG. 1. Sources of reactive oxygen species (ROS). ROS can be intracellulary generated by mitochondria and diverse NOX isoforms, peroxisome, endoplasmic reticulum (ER), xanthine oxidase, and lipogenase. It can also be applied from exogenous sources. Irrespective of its source, it may cause cell proliferation, differentiation, and/or cell cycle arrest, and this effect appears to be concentration dependent. Color images available online at www.liebertpub.com/scdCC BY-NC · PubMed Central
FIG. 2. Mitochondrial ROS production. The production of the superoxide anion, O2•−, by complex I and complex III in the matrix or the inter-membrane space forms H2O2 through the activity of SOD catalase dismutation. H2O2 can then be converted to H2O and O2 by glutathione peroxidase (GPX) and catalase or may play a second messenger role in essential signaling pathways. Color images available online at www.liebertpub.com/scd
FIG. 2. Mitochondrial ROS production. The production of the superoxide anion, O2•−, by complex I and complex III in the matrix or the inter-membrane space forms H2O2 through the activity of SOD catalase dismutation. H2O2 can then be converted to H2O and O2 by glutathione peroxidase (GPX) and catalase or may play a second messenger role in essential signaling pathways. Color images available online at www.liebertpub.com/scdCC BY-NC · PubMed Central
FIG. 3. NADPH oxidases. NOX enzymes reduce oxygen to O2•− by using pyridine nucleotide NADPH as an electron donor and molecular oxygen as an electron acceptor. ROS will be generated as the secondary product. A part of O2•− can directly react with nitric oxide (NO•) to form a toxic peroxynitrite. It can also be dismutated by superoxide dismutase to form hydrogen peroxide to induce cell signaling cascades or directly react with Fe3+ to form hydroxyl radical. Color images available online at www.liebertpub.com/scd
FIG. 3. NADPH oxidases. NOX enzymes reduce oxygen to O2•− by using pyridine nucleotide NADPH as an electron donor and molecular oxygen as an electron acceptor. ROS will be generated as the secondary product. A part of O2•− can directly react with nitric oxide (NO•) to form a toxic peroxynitrite. It can also be dismutated by superoxide dismutase to form hydrogen peroxide to induce cell signaling cascades or directly react with Fe3+ to form hydroxyl radical. Color images available online at www.liebertpub.com/scdCC BY-NC · PubMed Central
FIG. 4. ROS control signaling cascades involved in osteogenesis/adipogenesis. Wnt/β-catenin, MAPK (NELL-1), and Hh signaling induce osteogenesis while FOXO, PPARγ, and CEBPs signaling stimulate adipogenesis. BMP and IGF signaling have a dual effect in inducing both of these terminal fates. Induction of osteogenesis is optimal in the absence of ROS while induction of adipogenesis is optimal in the presence of ROS. Color images available online at www.liebertpub.com/scd
FIG. 4. ROS control signaling cascades involved in osteogenesis/adipogenesis. Wnt/β-catenin, MAPK (NELL-1), and Hh signaling induce osteogenesis while FOXO, PPARγ, and CEBPs signaling stimulate adipogenesis. BMP and IGF signaling have a dual effect in inducing both of these terminal fates. Induction of osteogenesis is optimal in the absence of ROS while induction of adipogenesis is optimal in the presence of ROS. Color images available online at www.liebertpub.com/scdCC BY-NC · PubMed Central
FIG. 5. ROS suppress important osteogenic signaling pathways while they promote adipogenic signaling pathways. Wnt/β-catenin and Hh signaling cascades induce osteogenesis and this is inhibited in the presence of high levels of ROS, which favors adipogenesis. MAPK signaling induces osteogenesis and is stimulated by ROS. In response to oxidative stress, FOXOs are phosphorylated and translocate to the nucleus where they attenuate the transcription of osteogenic genes while inducing adipogenic differentiation. The active form FOXO also induces the regulation of antioxidant and cell cycle arrest genes. The expression of antioxidants also increases adipogenic differentiation. Color images available online at www.liebertpub.com/scd
FIG. 5. ROS suppress important osteogenic signaling pathways while they promote adipogenic signaling pathways. Wnt/β-catenin and Hh signaling cascades induce osteogenesis and this is inhibited in the presence of high levels of ROS, which favors adipogenesis. MAPK signaling induces osteogenesis and is stimulated by ROS. In response to oxidative stress, FOXOs are phosphorylated and translocate to the nucleus where they attenuate the transcription of osteogenic genes while inducing adipogenic differentiation. The active form FOXO also induces the regulation of antioxidant and cell cycle arrest genes. The expression of antioxidants also increases adipogenic differentiation. Color images available online at www.liebertpub.com/scdCC BY-NC · PubMed Central

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Show all 16 references

Research works printed but not linked: 126

  1. 10.1093/geronj/11.3.298 · DOI · Paper page
  2. 10.1152/physrev.1998.78.2.547 · DOI · Paper page
  3. 10.1016/j.drudis.2006.04.003 · DOI
  4. 10.1089/ars.2011.4489 · DOI
  5. 10.1089/ars.2010.3405 · DOI
  6. 10.1186/1755-1536-4-20 · DOI
  7. 10.1186/ar614 · DOI
  8. 10.1007/s10517-005-0430-z · DOI
  9. 10.1182/blood-2003-05-1664 · DOI
  10. 10.1186/1478-811X-9-12 · DOI
  11. 10.1007/s12015-012-9365-8 · DOI
  12. 10.1089/ten.tec.2008.0031 · DOI
  13. 10.4252/wjsc.v4.i6.53 · DOI
  14. 10.1016/S1471-4914(01)02016-0 · DOI
  15. 10.1016/j.stem.2008.03.002 · DOI
  16. 10.1097/TP.0b013e3181c7dc99 · DOI
  17. 10.1002/jcb.20886 · DOI · Paper page
  18. 10.1089/scd.2010.0093 · DOI
  19. 10.1089/scd.2012.0306 · DOI
  20. 10.1196/annals.1402.075 · DOI
  21. 10.1016/j.scr.2013.07.004 · DOI
  22. 10.1186/scrt190 · DOI
  23. 10.1172/JCI21311 · DOI
  24. 10.1242/jcs.102.2.341 · DOI
  25. 10.1083/jcb.142.1.295 · DOI
  26. 10.1155/2013/684736 · DOI
  27. 10.1016/j.bbrc.2011.06.111 · DOI
  28. 10.1242/jcs.114.11.2085 · DOI
  29. 10.1038/nrrheum.2009.137 · DOI
  30. 10.1089/scd.2008.0130 · DOI
  31. 10.1007/s00467-004-1613-y · DOI
  32. 10.1016/0026-0495(95)90220-1 · DOI
  33. 10.1016/S0021-9258(19)76555-7 · DOI
  34. 10.1073/pnas.88.22.10045 · DOI
  35. 10.1515/CCLM.2008.302 · DOI
  36. 10.1016/j.mito.2011.02.001 · DOI
  37. 10.1161/01.RES.86.5.494 · DOI · Paper page
  38. 10.2174/138920112798868782 · DOI
  39. 10.1042/bj1280617 · DOI
  40. 10.1073/pnas.0506448103 · DOI
  41. 10.1161/01.RES.59.6.612 · DOI · Paper page
  42. 10.1016/0005-2760(94)90041-8 · DOI
  43. 10.1042/bj3180805 · DOI
  44. 10.1152/ajpheart.00515.2003 · DOI
  45. 10.1634/stemcells.2007-0509 · DOI
  46. 10.1016/j.freeradbiomed.2011.06.033 · DOI · Paper page
  47. 10.1074/jbc.M105395200 · DOI
  48. 10.1089/ars.2000.2.4-811 · DOI
  49. 10.1152/physrev.00018.2001 · DOI · Paper page
  50. 10.1073/pnas.0906805106 · DOI
  51. 10.1182/blood-2010-02-269894 · DOI
  52. 10.1038/276515a0 · DOI
  53. 10.1038/sj.bjp.0701171 · DOI
  54. 10.1139/y90-241 · DOI
  55. 10.1038/43459 · DOI · Paper page
  56. 10.1517/14728222.2011.628315 · DOI
  57. 10.1097/01.MIB.0000442012.45038.0e · DOI
  58. 10.1089/thy.2012.0003 · DOI
  59. 10.1089/ars.2006.1467 · DOI · Paper page
  60. 10.1002/jcp.20641 · DOI
  61. 10.1161/01.RES.0000135902.99383.6f · DOI
  62. 10.3727/096368910X507204 · DOI
  63. 10.1097/PRS.0b013e31824a2b19 · DOI
  64. 10.3727/096368912X639035 · DOI
  65. 10.1371/journal.pone.0077077 · DOI
  66. 10.1038/cddis.2013.117 · DOI
  67. 10.1165/rcmb.2006-0165OC · DOI
  68. 10.1016/S0891-5849(01)00610-4 · DOI
  69. 10.1006/bbrc.2001.5747 · DOI
  70. 10.1002/jcb.20497 · DOI
  71. 10.1182/blood-2004-09-3645 · DOI
  72. 10.1074/jbc.M702811200 · DOI
  73. 10.1074/jbc.M702810200 · DOI
  74. 10.1161/ATVBAHA.108.174219 · DOI
  75. Turker I, , Zhang YH, , Zhang YM, and Rehman J. (2007). Oxidative stress as a regulator of adipogenesis. Faseb J, 21:830.5.
  76. 10.1172/JCI21625 · DOI · Paper page
  77. 10.1007/s11010-014-2047-x · DOI
  78. 10.1179/135100009X392467 · DOI
  79. 10.1089/scd.2011.0516 · DOI
  80. 10.1074/jbc.M808742200 · DOI
  81. 10.1016/j.lfs.2011.06.007 · DOI
  82. 10.1194/jlr.M200305-JLR200 · DOI
  83. 10.1038/nature01657 · DOI
  84. 10.1038/nrm3198 · DOI · Paper page
  85. 10.1016/j.abb.2008.02.030 · DOI
  86. 10.1242/dev.02480 · DOI
  87. 10.1126/science.289.5481.950 · DOI
  88. 10.1016/j.bbrc.2003.12.073 · DOI
  89. 10.1172/JCI68049 · DOI
  90. 10.1126/science.1109083 · DOI
  91. Katoh M, and Katoh M. (2004). Human FOX gene family (Review). Int J Oncol, 25:1495–1500.
  92. 10.1016/j.ceb.2008.02.005 · DOI · Paper page
  93. 10.1016/S0070-2153(03)53002-2 · DOI · Paper page
  94. 10.1161/01.RES.0000147315.71699.51 · DOI
  95. 10.1038/nature03100 · DOI
  96. 10.1002/jcb.22846 · DOI
  97. 10.1172/JCI67603 · DOI
  98. 10.1016/j.tem.2008.09.002 · DOI
  99. Laudes M. (2011). Role of WNT signalling in the determination of human mesenchymal stem cells into preadipocytes. J Mol Endocrinol, 46:R65–R72.
  100. 10.1016/j.ceb.2007.09.014 · DOI
  101. 10.1359/JBMR.0301239 · DOI
  102. 10.1016/j.bbrc.2005.01.136 · DOI
  103. 10.1161/CIRCRESAHA.107.156372 · DOI
  104. 10.1111/j.1745-7254.2007.00671.x · DOI
  105. 10.1074/jbc.M407050200 · DOI
  106. 10.1074/jbc.M309069200 · DOI
  107. 10.1091/mbc.E08-06-0647 · DOI
  108. 10.1007/s11626-009-9230-5 · DOI
  109. 10.1016/S1534-5807(02)00401-X · DOI
  110. 10.1093/jn/134.11.2979 · DOI
  111. 10.1016/j.biochi.2007.08.012 · DOI
  112. 10.1016/j.cmet.2005.11.012 · DOI
  113. 10.1093/oxfordjournals.jhered.a022981 · DOI
  114. 10.1016/j.bone.2003.07.004 · DOI
  115. 10.1016/j.chembiol.2004.06.010 · DOI
  116. 10.1016/j.tem.2008.11.005 · DOI
  117. 10.1074/jbc.272.34.21473 · DOI
  118. 10.1242/jcs.079699 · DOI
  119. 10.3390/cells1040976 · DOI
  120. 10.1371/journal.pone.0048874 · DOI
  121. 10.1038/nature02583 · DOI
  122. 10.1016/j.cmet.2007.07.003 · DOI
  123. 10.1016/j.cmet.2011.08.007 · DOI
  124. 10.1016/S0014-5793(03)00862-7 · DOI
  125. 10.1016/j.bbamcr.2007.03.003 · DOI
  126. 10.3945/an.112.002626 · DOI

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Metadata

Authors
Atashi, F., Modarressi, A., & Pepper, M. S.
Affiliations
  • University Hospitals of Geneva
  • University of Geneva
Venue
Stem Cells and Development
Publisher
SAGE Publications
Published
2015-01-20
Volume
24
Issue
10
Pages
1150-1163
ISSN
  • 1547-3287
  • 1557-8534
DOI
10.1089/scd.2014.0484
PMC
PMC4424969
Cited by
603
References
16
Language
en
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