Display options
Cite
Sun X, Li X, Qi H, et al. MiR-21 nanocapsules promote early bone repair of osteoporotic fractures by stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells. J Orthop Translat. 2020;24:76-87doi: 10.1016/j.jot.2020.04.007.
Sun, X., Li, X., Qi, H., Hou, X., Zhao, J., Yuan, X., & Ma, X. (2020). MiR-21 nanocapsules promote early bone repair of osteoporotic fractures by stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells. Journal of orthopaedic translation, 2476-87. https://doi.org/10.1016/j.jot.2020.04.007
Sun, Xiaolei, et al. "MiR-21 nanocapsules promote early bone repair of osteoporotic fractures by stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells." Journal of orthopaedic translation vol. 24 (2020): 76-87. doi: https://doi.org/10.1016/j.jot.2020.04.007
Sun X, Li X, Qi H, Hou X, Zhao J, Yuan X, Ma X. MiR-21 nanocapsules promote early bone repair of osteoporotic fractures by stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells. J Orthop Translat. 2020 May 19;24:76-87. doi: 10.1016/j.jot.2020.04.007. eCollection 2020 Sep. PMID: 32695607; PMCID: PMC7349941.
Copy Download .nbib Format: NLM
Share it on

J Orthop Translat. 2020 May 19;24:76-87. doi: 10.1016/j.jot.2020.04.007. eCollection 2020 Sep.

MiR-21 nanocapsules promote early bone repair of osteoporotic fractures by stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells.

Journal of orthopaedic translation

Xiaolei Sun, Xueping Li, Hongzhao Qi, Xin Hou, Jin Zhao, Xubo Yuan, Xinlong Ma

Affiliations

  1. Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, China.
  2. Department of Orthopaedics, Tianjin Hospital, Tianjin, 300211, China.
  3. Institute for Translational Medicine, Qingdao University, Qingdao, 266021, China.

PMID: 32695607 PMCID: PMC7349941 DOI: 10.1016/j.jot.2020.04.007

Abstract

OBJECTIVE: The healing of osteoporotic fractures in the elderly patients is a difficult clinical problem. Currently, based on the internal fixation of fractures, the available drug treatments mainly focus on either inhibiting osteoclast function, such as bisphosphonate, calcitonin, oestrogen or promoting osteogenesis, such as parathyroid hormones. However, the availability of current antiosteoporotic drugs in promoting osteoporotic fracture healing is limited. The objective of the present study was to investigate the ability of the MiR-21/nanocapsule to enhance the early bone repair of osteoporotic fractures.

METHODS: Based on the presence of matrix metalloproteinases that are overexpressed at the fracture site, we designed the matrix metalloproteinase-sensitive nanocapsules which were formed by in situ free radical polymerisation on the surface of MiR-21 with 2-(methacryloyloxy) ethyl phosphorylcholine and the bisacryloylated VPLGVRTK peptide. The MiR-21/nanocapsule [n (miR-21)] and O-carboxymethyl chitosan (CMCS) were mixed until they formed a gel-like material [CMCS/n (miR-21)] with good fluidity and injectability. Thirty elderly Sprague Dawley (SD) rats (female, 14-month-old, 380 ± 10 g) were subjected to bilateral removal of the ovaries (ovariectomised). All rats were subjected to bilateral bone defects (2 mm diameter) of the proximal tibia and randomly divided into three groups (groups A, B, and C): separately injected with CMCS/n (miR-21), CMCS/n (NC-miR), and saline. Micro-computed tomography (CT) imaging was performed to evaluate newly formed bone volume and connectivity. Nondecalcified histology and toluidine blue staining were performed to measure the effects of CMCS/n (miR-21) on bone repair. In vitro, the effect of n (miR-21) on osteogenic differentiation to bone marrow mesenchymal stem cells (BMSCs) which derived from the ovariectomised rat model was observed.

RESULTS: The morphology of n (miR-21) was a regular spherical nanocapsule with a uniform small size (25-35 nm). The results confirmed that n (miR-21) could be efficiently phagocytosed by BMSCs and released in the cytoplasm to promote osteogenesis. The expression level of alkaline phosphatase and Runt-related transcription factor 2 mRNA in the n (miR-21) group was higher than that in the n (NC-miR) group. Animal experiments proved that CMCS/n (miR-21) produced better bone repair compared with the CMCS/n (NC-miR) group in the early stages of fracture healing at 4 weeks. In the late stage of fracture healing (8 weeks), micro-CT quantitative analysis showed that the new bone trabeculae in the CMCS/n (miR-21) group has decreased compared with the CMCS/n (NC-miR) group. In the CMCS/n (miR-21) group, the new cancellous bone had been absorbed, and the process of bone healing was almost completed. In contrast, the new bone in the CMCS/n (NC-miR) and the control groups was still in the healing process.

CONCLUSION: The cytological tests confirmed that n (miR-21) can promote osteogenic differentiation of BMSCs derived from the osteoporosis rat model. Furthermore, the results of animal tests demonstrated that local injection of CMCS/n (miR-21) promoted the early healing of osteoporotic bone defects. Consequently CMCS/n (miR-21) promoted the bone repair process to enter the moulding phase earlier.

THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: CMCS/n (miR-21) can be widely applied to elderly patients with osteoporotic fractures. This method can help patients with osteoporotic fractures recover earlier and avoid serious complications. It provides a potential approach for the clinical treatment of osteoporotic fractures in the elderly.

© 2020 Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society.

Keywords: Bone repair; MicroRNA-21; Nanocapsules; Osteoporotic fractures

References

  1. Eur J Pharm Biopharm. 2004 Sep;58(2):197-208 - PubMed
  2. Injury. 2016 Jun;47 Suppl 2:S21-6 - PubMed
  3. Bone. 2018 Sep;114:1-13 - PubMed
  4. Bone. 2020 Jan;130:115105 - PubMed
  5. Open Access Maced J Med Sci. 2019 Apr 14;7(7):1160-1165 - PubMed
  6. Osteoporos Int. 2018 Feb;29(2):521 - PubMed
  7. Planta Med. 2010 Jun;76(9):850-7 - PubMed
  8. J Bone Joint Surg Br. 2006 Jun;88(6):701-5 - PubMed
  9. Rheumatology (Oxford). 2018 Mar 1;57(3):583-584 - PubMed
  10. J Cell Physiol. 2018 Sep;233(9):6632-6643 - PubMed
  11. Adv Mater. 2015 Jan 14;27(2):292-7 - PubMed
  12. Eur Cell Mater. 2019 May 22;37:420-430 - PubMed
  13. Curr Osteoporos Rep. 2018 Feb;16(1):1-12 - PubMed
  14. Unfallchirurg. 2019 Jul;122(7):506-511 - PubMed
  15. Int J Pharm. 2018 May 30;543(1-2):160-168 - PubMed
  16. J Orthop Res. 2018 Jan;36(1):33-51 - PubMed
  17. Cell Physiol Biochem. 2016;38(1):40-8 - PubMed
  18. J Cell Biochem. 2013 Jun;114(6):1374-84 - PubMed
  19. Bull Exp Biol Med. 2008 Feb;145(2):259-62 - PubMed
  20. Spine (Phila Pa 1976). 2002 Aug 15;27(16 Suppl 1):S40-8 - PubMed
  21. Nat Rev Rheumatol. 2018 Jan;14(1):4 - PubMed
  22. Wiley Interdiscip Rev RNA. 2014 Mar-Apr;5(2):285-300 - PubMed
  23. Injury. 2016 Jan;47 Suppl 1:S10-4 - PubMed
  24. Nucleic Acids Res. 2018 Jan 4;46(D1):D360-D370 - PubMed
  25. Injury. 2018 Aug;49(8):1461-1465 - PubMed
  26. Arch Biochem Biophys. 2008 May 15;473(2):201-9 - PubMed
  27. Curr Osteoporos Rep. 2012 Jun;10(2):109-17 - PubMed
  28. J Orthop Res. 2015 Jul;33(7):957-64 - PubMed
  29. Exp Ther Med. 2019 Jan;17(1):709-714 - PubMed
  30. Biomarkers. 2014 Nov;19(7):553-6 - PubMed
  31. J Bone Joint Surg Am. 2002 Jun;84(6):1032-44 - PubMed

Publication Types