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NPJ Regen Med. 2021 Jun 07;6(1):32. doi: 10.1038/s41536-021-00141-3.

Multiomic analysis of stretched osteocytes reveals processes and signalling linked to bone regeneration and cancer.

NPJ Regenerative medicine

Lívia Santos, Aslihan Ugun-Klusek, Clare Coveney, David J Boocock

Affiliations

  1. Department of Sport Science, Sport, Health and Performance Enhancement Research Centre (SHAPE), School of Science and Technology, Nottingham Trent University, Nottingham, UK. [email protected].
  2. Department of Biosciences, Centre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, UK.
  3. John van Geest Cancer Research Centre, Centre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, UK.

PMID: 34099736 PMCID: PMC8184808 DOI: 10.1038/s41536-021-00141-3

Abstract

Exercise is a non-pharmacological intervention that can enhance bone regeneration and improve the management of bone conditions like osteoporosis or metastatic bone cancer. Therefore, it is gaining increasing importance in an emerging area of regenerative medicine-regenerative rehabilitation (RR). Osteocytes are mechanosensitive and secretory bone cells that orchestrate bone anabolism and hence postulated to be an attractive target of regenerative exercise interventions. However, the human osteocyte signalling pathways and processes evoked upon exercise remain to be fully identified. Making use of a computer-controlled bioreactor that mimics exercise and the latest omics approaches, RNA sequencing (RNA-seq) and tandem liquid chromatography-mass spectrometry (LC-MS), we mapped the transcriptome and secretome of mechanically stretched human osteocytic cells. We discovered that a single bout of cyclic stretch activated network processes and signalling pathways likely to modulate bone regeneration and cancer. Furthermore, a comparison between the transcriptome and secretome of stretched human and mouse osteocytic cells revealed dissimilar results, despite both species sharing evolutionarily conserved signalling pathways. These findings suggest that osteocytes can be targeted by exercise-driven RR protocols aiming to modulate bone regeneration or metastatic bone cancer.

References

  1. Redox Biol. 2019 Jan;20:167-181 - PubMed
  2. NPJ Regen Med. 2018 Oct 10;3:19 - PubMed
  3. Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16689-94 - PubMed
  4. Bone Res. 2013 Mar 29;1(1):27-71 - PubMed
  5. Bone. 2015 Jul;76:58-66 - PubMed
  6. Dis Model Mech. 2011 Mar;4(2):165-78 - PubMed
  7. Bone. 2020 Sep;138:115491 - PubMed
  8. Osteoporos Int. 2012 Apr;23(4):1225-34 - PubMed
  9. J Bone Miner Res. 2013 Nov;28(11):2357-67 - PubMed
  10. J Dent Res. 2006 Oct;85(10):905-9 - PubMed
  11. Nat Methods. 2013 Dec;10(12):1239-45 - PubMed
  12. J Bone Miner Res. 2012 May;27(5):1018-29 - PubMed
  13. J Biol Chem. 2006 Oct 20;281(42):31720-8 - PubMed
  14. J Natl Cancer Inst. 2021 Jan 4;113(1):54-63 - PubMed
  15. J Orthop Res. 2009 Oct;27(10):1280-7 - PubMed
  16. Front Endocrinol (Lausanne). 2014 Dec 09;5:208 - PubMed
  17. Med Biol Eng Comput. 2004 Jan;42(1):14-21 - PubMed
  18. Calcif Tissue Int. 2011 Jun;88(6):443-54 - PubMed
  19. Integr Biol (Camb). 2019 Apr 1;11(4):119-129 - PubMed
  20. J Clin Invest. 2017 Jun 30;127(7):2678-2688 - PubMed
  21. Nucleic Acids Res. 2019 Jan 8;47(D1):D711-D715 - PubMed
  22. Nat Rev Cancer. 2017 Sep 25;17(10):620-632 - PubMed
  23. J Hum Hypertens. 2011 May;25(5):311-9 - PubMed
  24. J Musculoskelet Neuronal Interact. 2006 Oct-Dec;6(4):408-17 - PubMed
  25. Exp Physiol. 2012 Jun;97(6):762-73 - PubMed
  26. Bone. 2008 Jan;42(1):172-9 - PubMed
  27. Nat Rev Endocrinol. 2019 Jun;15(6):339-355 - PubMed
  28. J Am Acad Orthop Surg. 2013 Dec;21(12):727-38 - PubMed
  29. Evol Med Public Health. 2016 May 21;2016(1):170-6 - PubMed
  30. Dev Cell. 2019 Jun 17;49(6):920-935.e5 - PubMed
  31. J Bone Miner Res. 1997 Dec;12(12):2014-23 - PubMed
  32. Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):E478-86 - PubMed
  33. Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450 - PubMed
  34. Cell Death Dis. 2020 Oct 12;11(10):846 - PubMed
  35. J Bone Miner Res. 2016 Dec;31(12):2215-2226 - PubMed

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