Display options
Cite
Iordachescu A, Hughes EAB, Joseph S, et al. Trabecular bone organoids: a micron-scale 'humanised' prototype designed to study the effects of microgravity and degeneration. NPJ Microgravity. 2021;7(1):17doi: 10.1038/s41526-021-00146-8.
Iordachescu, A., Hughes, E. A. B., Joseph, S., Hill, E. J., Grover, L. M., & Metcalfe, A. D. (2021). Trabecular bone organoids: a micron-scale 'humanised' prototype designed to study the effects of microgravity and degeneration. NPJ microgravity, 7(1), 17. https://doi.org/10.1038/s41526-021-00146-8
Iordachescu, Alexandra, et al. "Trabecular bone organoids: a micron-scale 'humanised' prototype designed to study the effects of microgravity and degeneration." NPJ microgravity vol. 7,1 (2021): 17. doi: https://doi.org/10.1038/s41526-021-00146-8
Iordachescu A, Hughes EAB, Joseph S, Hill EJ, Grover LM, Metcalfe AD. Trabecular bone organoids: a micron-scale 'humanised' prototype designed to study the effects of microgravity and degeneration. NPJ Microgravity. 2021 May 21;7(1):17. doi: 10.1038/s41526-021-00146-8. PMID: 34021163; PMCID: PMC8140135.
Copy Download .nbib Format: NLM
Share it on

NPJ Microgravity. 2021 May 21;7(1):17. doi: 10.1038/s41526-021-00146-8.

Trabecular bone organoids: a micron-scale 'humanised' prototype designed to study the effects of microgravity and degeneration.

NPJ microgravity

Alexandra Iordachescu, Erik A B Hughes, Stephan Joseph, Eric J Hill, Liam M Grover, Anthony D Metcalfe

Affiliations

  1. School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, UK. [email protected].
  2. Healthcare Technologies Institute, University of Birmingham, Edgbaston, Birmingham, UK. [email protected].
  3. School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, UK.
  4. Healthcare Technologies Institute, University of Birmingham, Edgbaston, Birmingham, UK.
  5. The Binding Site, Edgbaston, Birmingham, UK.
  6. School of Biosciences, College of Health and Life Sciences, Aston University, Birmingham, UK.

PMID: 34021163 PMCID: PMC8140135 DOI: 10.1038/s41526-021-00146-8

Abstract

Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface. The model is constructed with a combination of primary female osteoblastic and osteoclastic cells, seeded onto femoral head micro-trabeculae, where they recapitulate relevant phenotypes and functions. Subsequently, constructs are inserted into a simulated microgravity bioreactor (NASA-Synthecon) to model a pathological state of reduced mechanical stimulation. In these constructs, we detected osteoclastic bone resorption sites, which were different in morphology in the simulated microgravity group compared to static controls. Once encapsulated in human fibrin and exposed to analogue microgravity for 5 days, masses of bone can be observed being lost from the initial structure, allowing to simulate the bone loss process further. Constructs can function as multicellular, organotypic units. Large osteocytic projections and tubular structures develop from the initial construct into the matrix at the millimetre scale. Micron-level fragments from the initial bone structure are detected travelling along these tubules and carried to sites distant from the native structure, where new matrix formation is initiated. We believe this model allows the study of fine-level physiological processes, which can shed light into pathological bone loss and imbalances in bone remodelling.

References

  1. Nature. 2003 May 15;423(6937):337-42 - PubMed
  2. Calcif Tissue Int. 2003 Jun;72(6):698-709 - PubMed
  3. Nature. 2000 Jun 8;405(6787):704-6 - PubMed
  4. Ther Adv Musculoskelet Dis. 2012 Apr;4(2):61-76 - PubMed
  5. Proc Biol Sci. 2010 Jul 22;277(1691):2193-8 - PubMed
  6. Lancet. 2000 May 6;355(9215):1607-11 - PubMed
  7. Bonekey Osteovision. 2006 Oct;3(10):7-15 - PubMed
  8. Bone. 1996 Jul;19(1):13-21 - PubMed
  9. Bonekey Rep. 2014 Dec 10;3:614 - PubMed
  10. Sci Rep. 2017 Oct 13;7(1):13177 - PubMed
  11. Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3359-64 - PubMed
  12. PLoS One. 2013 Apr 18;8(4):e61372 - PubMed
  13. Mol Biol Cell. 2005 Jul;16(7):3100-6 - PubMed
  14. Nature. 2009 May 14;459(7244):262-5 - PubMed
  15. J Bone Miner Res. 1988 Aug;3(4):409-14 - PubMed
  16. Osteoporos Int. 2016 Feb;27(2):549-58 - PubMed
  17. J Bone Joint Surg Br. 1999 Jul;81(4):725-31 - PubMed
  18. J Spinal Cord Med. 2006;29(5):489-500 - PubMed
  19. Comp Med. 2008 Oct;58(5):424-30 - PubMed
  20. RSC Adv. 2018 Feb 13;8(14):7622-7632 - PubMed
  21. Sci Rep. 2017 Aug 3;7(1):7223 - PubMed
  22. J Bone Miner Res. 2004 Jun;19(6):1006-12 - PubMed
  23. Calcif Tissue Int. 2005 Feb;76(2):154-62 - PubMed
  24. J Vis Exp. 2011 May 06;(51): - PubMed
  25. Gastroenterology. 2011 Nov;141(5):1762-72 - PubMed
  26. Nature. 2015 Oct 22;526(7574):564-8 - PubMed
  27. Mol Cell Biol. 2014 Jan;34(1):16-29 - PubMed
  28. Sci Rep. 2016 Jan 28;6:20043 - PubMed
  29. Bone. 1996 May;18(5):443-50 - PubMed
  30. Cell. 2007 Aug 10;130(3):456-69 - PubMed
  31. Calcif Tissue Int. 1998 May;62(5):457-61 - PubMed
  32. Adv Sci (Weinh). 2019 Dec 10;7(2):1902295 - PubMed
  33. J Bone Miner Res. 1993 Dec;8 Suppl 2:S565-72 - PubMed
  34. Life Sci. 2016 May 1;152:82-93 - PubMed
  35. Nature. 2020 Jun;582(7812):399-404 - PubMed
  36. J Bone Miner Res. 1998 Oct;13(10):1594-601 - PubMed
  37. Gene. 2005 Nov 21;361:38-56 - PubMed
  38. J Bone Miner Res. 2002 Mar;17(3):455-64 - PubMed
  39. J Bone Miner Res. 1999 Nov;14(11):1934-42 - PubMed
  40. Bone. 2008 Apr;42(4):606-15 - PubMed
  41. J Musculoskelet Neuronal Interact. 2003 Dec;3(4):290-1; discussion 292-4 - PubMed
  42. Proc Biol Sci. 2014 Mar 12;281(1782):20140192 - PubMed
  43. Nature. 2013 Sep 19;501(7467):373-9 - PubMed
  44. Cell Metab. 2019 Nov 5;30(5):890-902.e8 - PubMed
  45. PLoS One. 2009;4(5):e5393 - PubMed
  46. Genes (Basel). 2018 May 10;9(5): - PubMed
  47. Nat Cell Biol. 2017 May;19(5):568-577 - PubMed
  48. Bone. 1987;8(6):351-5 - PubMed
  49. Bone Res. 2016 Oct 18;4:16041 - PubMed
  50. Dis Model Mech. 2019 Jul 29;12(7): - PubMed
  51. J Bone Miner Metab. 2007;25(1):46-53 - PubMed
  52. FASEB J. 2005 Nov;19(13):1842-4 - PubMed
  53. Int J Mol Sci. 2020 Jan 30;21(3): - PubMed
  54. J Bone Joint Surg Br. 2010 Oct;92(10):1325-31 - PubMed
  55. J Biol Chem. 2003 Jun 27;278(26):24113-7 - PubMed
  56. J Bone Miner Res. 2000 May;15(5):919-26 - PubMed
  57. Sci Rep. 2020 Aug 13;10(1):13751 - PubMed
  58. PLoS One. 2011;6(10):e25900 - PubMed
  59. NPJ Microgravity. 2021 Feb 8;7(1):2 - PubMed
  60. Semin Cancer Biol. 2005 Oct;15(5):378-86 - PubMed
  61. Lab Invest. 2017 Oct;97(10):1235-1244 - PubMed
  62. J Musculoskelet Neuronal Interact. 2001 Mar;1(3):193-207 - PubMed
  63. Bone. 2015 Feb;71:189-95 - PubMed
  64. Am J Physiol Renal Physiol. 2001 Jul;281(1):F12-25 - PubMed
  65. J Bone Miner Res. 2011 Feb;26(2):229-38 - PubMed
  66. Bone Rep. 2015 Apr 17;2:59-67 - PubMed
  67. Nat Med. 2011 Sep 11;17(10):1231-4 - PubMed
  68. Sci Rep. 2017 Mar 21;7:44999 - PubMed
  69. PLoS One. 2015 Sep 22;10(9):e0138189 - PubMed
  70. Nat Rev Rheumatol. 2012 Jan 31;8(3):133-43 - PubMed
  71. Cell Stem Cell. 2018 Dec 6;23(6):787-793.e6 - PubMed
  72. Oncotarget. 2015 May 10;6(13):10801-11 - PubMed
  73. Nat Biotechnol. 2000 Sep;18(9):954-8 - PubMed
  74. J Neuroimmunol. 2010 Feb 26;219(1-2):90-9 - PubMed
  75. Development. 1996 May;122(5):1611-20 - PubMed
  76. J Cell Biochem. 2013 Aug;114(8):1901-1907 - PubMed
  77. Bone. 1993 Nov-Dec;14(6):877-83 - PubMed
  78. Bone. 1989;10(3):187-94 - PubMed
  79. Cell. 2018 Nov 29;175(6):1591-1606.e19 - PubMed
  80. Sci Rep. 2017 Jun 6;7(1):2811 - PubMed
  81. Front Endocrinol (Lausanne). 2018 May 14;9:236 - PubMed
  82. Curr Opin Pharmacol. 2015 Jun;22:41-50 - PubMed
  83. J Osteoporos. 2011;2011:293808 - PubMed
  84. J Mech Behav Biomed Mater. 2015 Apr;44:61-70 - PubMed
  85. Endocrinol Metab Clin North Am. 2012 Jun;41(2):323-33, vi - PubMed
  86. Front Bioeng Biotechnol. 2018 Oct 11;6:134 - PubMed
  87. Arch Osteoporos. 2013;8:136 - PubMed
  88. Exp Cell Res. 1996 Apr 10;224(1):103-9 - PubMed
  89. Cell Metab. 2007 Jun;5(6):464-75 - PubMed
  90. Int J Mol Sci. 2018 Aug 03;19(8): - PubMed
  91. PLoS One. 2016 Jun 08;11(6):e0156991 - PubMed
  92. Bone. 2013 Jun;54(2):250-7 - PubMed
  93. FASEB J. 2009 Aug;23(8):2549-54 - PubMed
  94. Osteoporos Int. 2015 Nov;26(11):2665-76 - PubMed
  95. Sci Rep. 2020 Sep 23;10(1):15562 - PubMed
  96. Curr Protoc Stem Cell Biol. 2019 Feb;48(1):e79 - PubMed

Publication Types

Grant support